Category: 8. Health

A groundbreaking study shows that two repurposed cancer drugs, when combined, can correct complex brain cell dysfunction and restore memory in Alzheimer’s mouse models, offering hope for new multi-targeted therapies.

​​​​​​​Study: Cell-type-directed network-correcting combination therapy for Alzheimer’s disease. ​​​​​​​Image Credit: Kateryna Kon / Shutterstock

In a recent study published in the journal Cell, a group of researchers investigated whether combining the aromatase inhibitor letrozole and the topoisomerase I inhibitor irinotecan could reverse cell–type–specific transcriptomic disturbances and improve cognition and pathology in Alzheimer’s disease (AD) models.

Background

Every three seconds, someone develops dementia, and more than 50 million people worldwide now live with AD, a figure forecast to triple by 2050. Existing monoclonal antibodies slow amyloid beta (Aβ) accumulation yet leave most patients cognitively impaired, partly because AD involves intertwined neuronal and glial dysfunctions.

Recent single-nucleus RNA sequencing (snRNA-seq) studies have revealed that excitatory neurons, inhibitory neurons, microglia, astrocytes, and oligodendrocyte precursor cells (OPCs) each follow distinct yet interacting degenerative programs.

Repurposing approved drugs offers a faster, safer route to intervention, but single-target candidates rarely tackle this cellular heterogeneity. Therefore, the correction of multi-cell-type networks warrants exploration.

The study identified 25 drugs with predicted multi-cell-type effects, but only five showed a reduced AD risk in human clinical records, including letrozole and irinotecan, which were prioritized for their complementary neuronal and glial targeting. Further research should determine whether dual-action regimens translate into durable clinical benefit and address the sex-specific responses observed in preclinical models.

About the Study

Investigators first mined integrated human post-mortem snRNA-seq datasets from three independent studies to generate cell-specific AD expression signatures. They then matched these against the Connectivity Map (CMap) compendium, a database of drug perturbations primarily using cancer cell lines, to identify drugs whose perturbation profiles inversely correlated with disease patterns.

Electronic Medical Record (EMR) analytics of 1.4 million adults aged ≥ 65 years across six University of California health systems revealed that exposure to letrozole or irinotecan correlated with a lower AD incidence after propensity-matched adjustment for demographics, comorbidities, and cancer indications.

Notably, cancer patients have lower baseline AD risk, and letrozole’s effects in males were inconclusive due to limited data.

To validate causality, researchers crossed 5xFAD amyloid-overproducing mice with P301S mutant tau transgenic (PS19) mice. They allocated 20 sex-balanced, double-transgenic animals to each of four groups: vehicle, letrozole (1 mg/kg), irinotecan (10 mg/kg), or the combination, administered every other day by intraperitoneal injection for three months, starting at 4–5 months of age.

Morris water maze assessed spatial learning, while brains underwent Sudan Black volumetry, Thioflavin S Aβ staining, AT8 phosphorylated tau (p-tau) immunofluorescence, Iba1 microglial and GFAP astrocytic histology, plus NeuN neuronal counts. Parallel hippocampal snRNA-seq libraries were prepared using 10x Genomics’ Chromium technology and analyzed with UMAP clustering to map drug-induced transcriptomic shifts.

Study Results

During six days of hidden platform training, swim latencies did not differ between groups, confirming equal baseline performance across the two groups. In probe trials, only combination-treated mice spent significantly more time and made more crossings in the target quadrant at both 24 hours and 72 hours, demonstrating recovery of both short- and long-term spatial memory. In contrast, single agents showed partial benefit in males, while females saw negligible improvement. Visual acuity and motility were unchanged, excluding sensorimotor confounds.

Morphologically, all treatments reduced hippocampal atrophy, but the combination achieved the greatest volume preservation. Aβ plaque burden fell across groups, yet p-tau deposition declined only with dual therapy, aligning with its unique cognitive efficacy.

Irinotecan, alone or in combination, reduced microgliosis (Iba1 area), and letrozole monotherapy significantly rescued CA1 neuronal loss, whereas astrocytosis (GFAP) dropped modestly under irinotecan alone. Mechanistically, letrozole preserved neurons while irinotecan tempered glial inflammation – effects that combined additively.

At the transcriptomic level, combination therapy expanded the proportions of CA1 and CA3 pyramidal neurons within hippocampal nuclei. Cell-cell communication analysis showed dampened hyperactive signaling from glia to neurons. Across six major cell types, the regimen counterregulated AD signature genes, notably normalizing APOE expression in microglia, astrocytes, and OPCs.

Gene ontology enrichment tied reversed neuronal genes to estrogen signaling and synaptic plasticity, aligning with letrozole’s aromatase blockade, while glial reversals highlighted oxidative stress mitigation and cholesterol transport, consonant with irinotecan’s anti-inflammatory profile.

Conclusions

To summarize, the letrozole-irinotecan combination delivered a convergent, cell-type-directed therapy that surpassed either monotherapy by restoring memory, shrinking Aβ plaques, lowering p-tau deposition, dampening microgliosis and astrocytosis, and preserving hippocampal neurons. snRNA-seq confirmed the regimen rewired disease-specific gene networks across neurons and glia.

These preclinical results, tempered by methodological caveats (e.g., cancer-cell-derived drug signatures), support repurposed multi-target strategies for AD and justify clinical trials testing this affordable anticancer duo in at-risk populations, with a focus on sex-specific efficacy.

Most post-weaning sampling relies on oral fluid samples since jugular venipuncture can be time-consuming and requires skilled personnel. Assessing whether easy to collect post-mortem samples can provide value for diagnosis and monitoring in the post-weaning stages is necessary as this methodology can be adopted by industry when resources are scarce, even though they are not the gold standard specimen.

Those samples are:

• Tongue tip fluid (TTF),
• Intracardiac blood (IC),
• Oral/nasal swabs (ONS),
• Rectal swabs (RS),
• Superficial inguinal lymph nodes (SILN)

The objectives of a study by C.M. Melini and colleagues at the University of Minnesota were:

1) Assess the sensitivity and specificity of TTF, ONS, and SILN in growing pigs when compared to IC, in presence of porcine reproductive and respiratory syndrome virus (PRRSV),

2) Describe detection of porcine circovirus type 2 and 3 (PCV-2, PCV-3), porcine parvovirus type 1 and 2 (PPV-1, PPV-2), Lawsonia intracellularis (Li), and Influenza A virus (IAV), through RT-PCR of collected post-mortem samples (e.g., TTF, ONS, RS, SILN). The results of the study were presented at the 2024 North American PRRS Symposium.

One wean-to-finish farm group of pigs undergoing a PRRS outbreak was sampled when animals were 5 weeks of age (WOA) and 11 WOA. A second group of growing pigs undergoing a similar health challenge was sampled at the grow-finish farm at 15 WOA at a different location. During each sampling event, 30 dead pigs were included in the study for a total sample of 90 pigs.

Besides TTF, the other collected post-mortem specimens were IC (for PRRSV), ONS (for IAV and PRRSV), RS (for PPV and Li), SILN (for PCV and PRRSV), all samples were tested individually through RT-PCR. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) were calculated for PRRSV. Proportion of RT-PCR positive results from sample types tested for other pathogens were compared by descriptive statistics.

All pathogens were detected at least once in TTF with Ct values ranging from 11.6 to 39.8. PRRSV, PCV2/PCV3, PPV1/PPV2, Li, and IAV were detected in 96%, 22%, 49%, 6%, and 38% of the TTF samples, respectively.

For PPRSV the best results for all sample type comparison were at 11 WOA: TTF had Se=84%, Sp=9%, PPV=62%, NPV=25%, ONS had Se=74%, Sp=73%, PPV=82%, NPV=62%, and SILN had Se=100%, Sp=9%, PPV=66%, NPV=100%. PCV2/PCV3 was detected in 6% of SILN samples. PPV1/PPV2 was detected in 31% of the RS samples. Li was detected in 0% of the RS samples. IAV was detected in 38% of the ONS samples.

Different pathogens were detected using TTF samples at three different ages during the growth and finishing phases of the pigs, as well as in other sample types such as ONS, RS, SILN, and IC. Detection can vary according to the assessed pathogen and the age of the pigs. However, the overall diagnostic performance of the specimens used still requires further investigation. Indeed, complete and exhaustive collection of multiple clinical specimens from different body systems remains the standard in diagnostic investigations.

GENEVA: The World Health Organisation warned on Tuesday a major chikungunya virus epidemic risks sweeping around the globe, calling for urgent action to prevent it.

The WHO said it was picking up exactly the same early warning signs as in a major outbreak two decades ago and wanted to prevent a repeat. Chikungunya is a mosquito-borne viral disease that causes fever and severe joint pain, which is often debilitating. In some cases it can be deadly.

“Chikungunya is not a disease that is widely known, but it has been detected and transmitted in 119 countries globally, putting 5.6 billion people at risk,” said the WHO’s Diana Rojas Alvarez.

She recalled how from 2004 to 2005, a major chikungunya epidemic swept across the Indian Ocean, hitting small island territories before spreading globally and affecting almost half a million people.

“Today, WHO is seeing the same pattern emerge: since the beginning of 2025, Reunion, Mayotte and Mauritius have all reported major chikungunya outbreaks.

One-third of the population of Reunion is estimated to have been infected already,” she told a press briefing in Geneva. The symptoms of chikungunya are similar to those of dengue fever and Zika virus disease, making it difficult to diagnose, according to the WHO.

Rojas Alvarez said that like 20 years ago, the virus was now spreading to other places in the region, such as Madagascar, Somalia and Kenya. “Epidemic transmission is also occurring in south Asia,” she added.

In Europe, imported cases have also been reported, linked with the outbreak in the Indian Ocean islands. Local transmission has been reported in France, and suspected cases detected in Italy.

Published in Dawn, July 23rd, 2025

QUETTA: On the outskirts of Quetta, a two-year-old boy named Ayaan clutches his mother’s hand, his eyes lighting up at the sight of a colorful swing — the centrepiece of a local initiative known as the Immunity Express. To a casual observer, it’s a simple source of childhood joy. But for health workers and local leaders in Balochistan, it symbolises something far greater: hope in the fight against polio.

The Immunity Express initiative in Balochistan is part of the broader Pakistan Polio Eradication Programme, aiming to reach children in high-risk areas with the polio vaccine. This initiative uses creative methods, like incorporating fun activities and community engagement, to encourage vaccination and ensure children receive the life-saving vaccine in high-risk areas of Quetta.

Under the initiative polio teams in high-risk areas of Quetta are using camel rides, swings, and fun-filled activities to attract children and ensure they receive the life-saving polio vaccine.

In a province long challenged by persistent poliovirus transmission, 2025 is offering the most encouraging signs yet. As of July, Balochistan has not reported a single case of wild poliovirus. And according to the Emergency Operations Centre (EOC), the prevalence of the virus in environmental samples has sharply declined.

Initiative part of broader polio eradication programme

In June 2025, just 4 out of 23 environmental samples (17 per cent) across the province tested positive for poliovirus. In the high-risk Quetta Block, an area considered a traditional epicenter of transmission, only one out of seven samples (14 per cent) showed traces of the virus. This marks the lowest level of virus detection in over 18 months.

“This progress reflects the resilience and dedication of everyone involved, from health workers to community leaders,” said Inamul Haq, Coordinator of the Emergency Operations Centre in Balochistan.

Health officials attribute the success to a coordinated, community-wide effort. Religious leaders have promoted vaccination from pulpits and community gatherings. Media campaigns have pushed back against misinformation, while development partners provided vital technical and logistical support. At the core of it all, the government of Balochistan and district administrations have demonstrated strong leadership, ensuring that each vaccination campaign is thoroughly planned, funded, and monitored.

Initiatives like Immunity Express, social mobiliser programmes, and journalist engagement sessions have played a critical role in improving vaccine uptake — especially in historically underserved or vaccine-hesitant communities.

“Environmental sample positivity is declining, and that gives us hope,” said Mr Haque. “But the virus still lurks. The moment we become complacent, it will strike again.”

While the battle against polio is far from over, the absence of reported cases in 2025 and the downward trend in environmental detections point to real momentum in Balochistan’s efforts to end the disease.

As Ayaan laughs and swings with carefree delight, he represents more than a healthy child — he is a symbol of what’s possible when communities, institutions, and governments come together.

Published in Dawn, July 23rd, 2025

If you like to have a glass of wine or a cocktail every now and then but also take certain medications, you may have wondered if you shouldn’t be mixing them. Well, we’ve got you covered. 

When it comes to drinking alcohol, there are plenty of warnings that come with it and guidance on how to do it responsibly. One of the most common warnings we tend to see is not to mix alcohol with medications. But what exactly does this mean? Does this mean you shouldn’t take a pill and sip on an alcoholic beverage at the same time? Does this mean that you shouldn’t drink alcohol if you’re regularly taking medication? And what medications could actually be negatively affected? There are a lot of questions surrounding this particular warning, so we decided to ask medical doctors about what you really need to know about how alcohol can affect your medication.

“Alcohol and medication can interact in different ways based on the medication and the individual’s physiology,” says Thomas Pontinen, M.D., co-founder of MAPS, an interventional pain management clinic based in Chicago. “Many medications can become less effective with alcohol, which can be of concern for individuals who need their medication to stay healthy. This is because alcohol can affect the body’s ability to absorb medication.”

Here’s the science behind which medications don’t mix well with alcohol and what happens to your body—and the effectiveness of the medication—when you do drink alcohol while taking them.

How Alcohol and Medication Interact

“Alcohol should be avoided while taking medication because, in general, it can make side effects worse, diminish the intended benefit of the medication, and threaten the health and well-being of the individual taking it,” Pontinen explains. “It’s also important to mention that alcohol and many medications are metabolized by the liver, so combining them can put a lot of stress on the essential organ and worsen other conditions like liver disease.”

“There are a range of side effects and symptoms that may occur, including change in blood pressure, fainting, change in behavior, maybe even nausea and vomiting or dizziness and headaches,” says Laura Purdy, M.D., a board-certified family medicine physician and the medical director at EXILERA. “When it comes to operating heavy machinery and driving a car, there are additional concerns because lack of coordination, change in mood, emotion and behavior can also be an issue. The effects might be stronger than you are used to, and you may feel more impaired after having one drink than you would typically plan for. Bottom line, your body can respond totally differently then, when both are consumed versus when just taking medications.”

Here are 7 medications that shouldn’t be mixed with alcohol:

1. Pain Relievers

“When alcohol is mixed with medications such as acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin or ibuprofen, liver damage and gastrointestinal bleeding can be a result,” says Katy Dubinsky, Pharm.D., a pharmacist and the founder and CEO of Vitalize.

2. Antidepressants

According to Purdy, antidepressants won’t be as effective when mixed with alcohol, and in some cases, could even make symptoms worse. This includes selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). Dubinsky explains that mixing the two can also make you feel more sleepy and less coordinated.

3. Antibiotics

“Taking certain antibiotics with alcohol might have serious side effects, such as headaches, flushing and nausea,” says Dubinsky. “Examples of these include metronidazole and tinidazole.”

In particular, alcohol causes dehydration in the body by inhibiting the release of vasopressin. Because getting enough fluids is vital for fighting an infection, drinking alcohol isn’t advised because of the ways it can make symptoms worse—and prolong recovery.

4. Antipsychotics

“Alcohol may intensify the sedative effects of antipsychotic drugs, causing impairments in mental and physical abilities,” Dubinsky explains. Some of the more common symptoms of mixing the two include difficulty breathing, low blood pressure, fainting and, in severe cases, seizures or coma.

5. Anxiety Medication and Sedatives

Alcohol coupled with drugs like benzodiazepines (Xanax and Valium) and sleep aids (Ambien) can result in extreme drowsiness, respiratory difficulties and potentially life-threatening sedation, according to Dubinsky.

“Anxiety medications and alcohol consumption can cause abnormal behaviors, loss of memory and motor function control and, as with sleeping medications, difficulties breathing normally,” says Purdy.

6. Diabetes Medication

Alcohol’s interference with certain medications can put someone with diabetes at risk for low or high blood sugar, depending on what drink is consumed and the medication. Additionally, certain alcoholic beverages like beer and sweetened mixed drinks are high in carbohydrates, which can negatively affect a person’s blood sugar levels.

Symptoms of low blood sugar include double or blurry vision, sweating, tingling and numbness, tiredness or trouble sleeping, fast or pounding heartbeat, shaking or trembling, unclear thinking and more. The symptoms of high blood sugar to watch out for are feeling thirsty, tired or weak, headaches, peeing frequently and blurred vision.

Dubinsky says this can occur for diabetes drugs such as insulin or sulfonylureas.

7. Blood Thinners

Blood thinners, also known as anticoagulants or antiplatelet drugs, help prevent blood from clotting. People with certain heart conditions or congenital heart defects or those preparing for surgery take these medications. “Drinking alcohol may interfere with the way warfarin and other blood thinners function, increasing the risk of clotting or bleeding,” says Dubinsky. 

Additional Consequences

While these particular medications are important to keep in mind before consuming alcohol, in general, Purdy warns that there could be other underlying health conditions that could result in adverse (or even life-threatening) side effects when mixing the two.

“In some situations, the end result could be deadly, or overdosing can be a concern,” warns Purdy. “If you have any underlying health conditions that you take medications for, or maybe are not aware of, there could be additional side effects and new symptoms that you could experience that could be life-threatening.”

Plus, alcohol can make medicine less effective or even useless, and in some cases, it can react poorly with certain ingredients that are in your medications.

How to Stay Safe

No matter the medication—whether it’s prescribed, over-the-counter or otherwise—Pontinen says it’s important to speak with your doctor about the side effects before safely consuming alcohol.

“Combining medication and alcohol can be dangerous and even life-threatening, so do not willingly take risks and be sure to avoid alcohol while taking medication unless you’re sure it’s safe,” he says. “Individuals who are under heavy sedative effects need to be monitored to make sure they do not risk injury or choking.”

But what if you do consume alcohol while you’re on medication? Pontinen says it’s important to be in close contact with a loved one in case you fall out of consciousness. “If you begin to experience severe symptoms of headache, gastrointestinal pain, nausea, dizziness or drowsiness after combining medication with alcohol, seek medical attention immediately and remain with a loved one who is prepared to help if need be until medical help arrives.”

Our Expert Take

There’s a reason medical professionals recommend not consuming alcohol while on regular medication, especially medications such as pain relievers, antidepressants, antibiotics, antipsychotics, sedatives, diabetes medications and blood thinners. Not only could the medication not be as effective when mixed with alcohol, but your body could react poorly to the combination of the two. 

The side effects of mixing alcohol with medications could range from mild to severe, with some even being life-threatening. This why it’s crucial to speak to a doctor before drinking alcohol while taking regular medication—whether it’s a prescription or over-the-counter. If you do consume alcohol, be sure to connect with a trusted friend or family member to ensure that you’re not alone if adverse side effects occur or if you need to seek medical attention.

DALLAS – July 22, 2025 – A team led by UT Southwestern Medical Center researchers has uncovered the atomic structure of a protein complex pivotal to the function of motile cilia, the hair-like structures extending from the surfaces of many cell types that generate their movement.

The researchers’ findings involving radial spoke 3 (RS3), reported in Nature Structural & Molecular Biology, help answer some fundamental questions about how motile cilia work and could eventually lead to new treatments for ciliopathies, diseases in which cilia’s structure and/or function are impaired. These include primary ciliary dyskinesia, a life-shortening genetic disorder that causes infertility, chronic respiratory problems, reversed organ placement, and excess brain fluid.

“Our findings reveal RS3 as a unique hub connecting mechanical support with energy production and recycling in these highly conserved, motion-generating organelles,” said Daniela Nicastro, Ph.D., Professor of Cell Biology at UT Southwestern. Dr. Nicastro co-led the study with Xuewu Zhang, Ph.D., Professor of Pharmacology and Biophysics, and first author Yanhe Zhao, Ph.D., Research Scientist in the Nicastro Lab.

Cilia are ubiquitous on cells, playing a variety of roles, Dr. Nicastro explained. While non-motile cilia serve as sensors for chemical and mechanical signals, motile cilia rhythmically beat to propel some types of cells through fluid or to move small objects and fluid in their environment and across tissues.

Scientists have long known that the oscillatory beating of a motile cilium is generated by thousands of molecular motor proteins called dyneins. But how cells coordinate their actions to whip cilia back and forth and where the energy driving this motion comes from has been unclear.

To help answer these questions, researchers at UTSW and elsewhere have investigated the structures of various protein complexes that make up motile cilia’s inner workings. Most of these studies have used model organisms, such as the single-celled green algae Chlamydomonas, that move through their aquatic habitats with two motile cilia.

Three of these ciliary complexes compose structures called radial spokes, which repeat many times along the length of cilia and connect the peripheral microtubule-cylinder that holds the dynein motors to a central spine, so that in cross-section the radial spokes look like the spokes of a wheel. While the structures of Chlamydomonas’ radial spoke complexes 1 and 2 (RS1 and RS2) mirror those found in mammals, including humans, the algal RS3 is much shorter than the mammalian complex. Studies by the Nicastro Lab have shown patients carrying mutations that affect RS1 and RS2 but leave RS3 intact have less severe ciliopathies than those where RS3 is also affected, suggesting RS3 is uniquely important for cilia function. However, RS3’s molecular structure had been unknown.

To solve the mammalian RS3 structure, Drs. Nicastro, Zhang, and Zhao and their colleagues used a variety of approaches to study mouse RS3, including high-tech imaging from cryo-electron microscopy (cryo-EM) and cryo-electron tomography as well as proteomics and computational biology. Their investigation revealed that mammalian RS3 is made of 14 proteins, 10 of which were previously unknown to be part of this complex. By matching these proteins to those in a comprehensive mouse protein database, the researchers identified them and their functions.

Dr. Zhao said several of RS3’s proteins are involved in placing or removing phosphate groups from other proteins – a regulatory function that he and his colleagues suspect plays a part in coordinating the activity of the dynein motors. Several other proteins in this complex are involved in generating ATP, a fuel that cells use for energy and that drives dynein motion. Together, he said, these findings suggest RS3’s components are pivotal for both synchronizing dynein activity and powering the motors’ motion in cilia.

RS3’s structure could act as a blueprint for designing drugs that modify its activity, Dr. Zhang said. Such therapies could eventually be used to treat ciliopathies such as polycystic kidney disease and primary cilia dyskinesia. The researchers plan to continue investigating the individual roles and interactions of proteins that make up RS3 and how this structure might differ among species.

Dr. Nicastro played a pivotal role in establishing UTSW’s Cryo-EM Facility, which she directed until December 2019. Dr. Zhang is a Virginia Murchison Linthicum Scholar in Medical Research.

This study was funded by grants from the National Institutes of Health (R01GM083122 and R35GM130289) and the Cancer Prevention and Research Institute of Texas (RR140082).

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 24 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may be more effective than metformin for reducing the risk of dementia in patients with type 2 diabetes, according to findings from a recent study.¹

Leveraging a decade of data from the TriNetX database for adults with type 2 diabetes who initiated either GLP-1 RAs or metformin as first-line therapy, the study found GLP-1 RAs significantly reduced the risk of overall dementia—particularly Alzheimer’s disease and non-vascular dementias—compared with metformin. Notably, GLP-1 RAs also provided substantial reductions in all-cause mortality, further supporting the early use of GLP-1 RAs in patients with type 2 diabetes at risk of cognitive decline.¹

Previous research has indicated a heightened risk of developing dementia among individuals with type 2 diabetes, with dementia risk increasing the longer a person has diabetes and the more severe it is.2 While both GLP-1 RAs and metformin have both demonstrated potential neuroprotective effects in type 2 diabetes, no head-to-head real-world comparisons have evaluated their relative efficacy in preventing dementia.¹

“Given the significant clinical and societal burden of T2DM-related dementia, determining which therapy— GLP-1 RAs or metformin—provides superior protection against cognitive decline is crucial,” senior author Jiaqiang Zhang, of the department of anesthesiology and perioperative medicine at Zhengzhou University, and colleagues wrote.¹ “Clarifying this therapeutic distinction will offer crucial guidance for clinicians, policymakers, and researchers, potentially reshaping dementia prevention strategies in T2DM management.”

To assess the comparative effectiveness of GLP-1 RAs and metformin in reducing dementia risk, investigators conducted a retrospective cohort study using data from TriNetX for adults with type 2 diabetes who initiated either GLP-1 RAs or metformin as first-line therapy between November 2004 and November 2024. The index date was defined as the earliest prescription date post-diagnosis, with ≥ 24 months of follow-up required. Investigators employed 1:1 propensity score matching to balance baseline characteristics between patients on GLP-1 RAs and patients on metformin.¹

The primary outcome was the incidence of overall dementia, defined as the first occurrence of a diagnosis of vascular dementia, Alzheimer’s disease, unspecified dementia, or dementia associated with other diseases. Secondary outcomes included the incidence of specific dementia subtypes and all-cause mortality.¹

To address potential biases from pre-existing or undiagnosed dementia and to allow sufficient time for the therapeutic effects of the medications to manifest, investigators applied a 6-month washout period. Follow-up began on day 181 after the index date and continued until the first occurrence of an outcome, loss to follow-up, or the conclusion of the study period.¹

Among 87,229 matched patients per cohort, GLP-1 RA use was associated with a significantly reduced risk of overall dementia (adjusted hazard ratio [aHR], 0.90; 95% CI, 0.85-0.95), Alzheimer’s disease (aHR, 0.88; 95% CI, 0.83-0.94), and non-vascular dementias (aHR, 0.75; 95% CI, 0.70-0.81) compared with metformin. However, no significant difference was observed for vascular dementia. Further analysis revealed the all-cause mortality rate was notably reduced in the GLP-1 RA group (aHR, 0.89; 95% CI, 0.81-0.95).¹

Subgroup analyses showed consistent benefit across age and sex. Investigators noted the benefits were most pronounced in patients aged ≥60 years, with significant reductions noted in those 60–79 years of age (aHR, 0.85; 95% CI, 0.80-0.90) and ≥ 80 years of age (aHR, 0.80; 95% CI, 0.74-0.88). Additionally, while both sexes benefitted, investigators pointed out females had a slightly lower aHR (0.83; 95% CI, 0.79-0.89) compared with males (0.90; 95% CI, 0.84-0.97).¹

“Given the increasing global burden of diabetes-related cognitive decline and the lack of head-to-head comparisons between GLP-1 RAs and metformin, our findings provide actionable insights for clinical decision-making and may inform future guidelines. Additionally, the study underscores the importance of tailoring therapeutic strategies to optimize both metabolic and neuroprotective outcomes in high-risk T2DM populations,” investigators concluded.¹ “Further randomized controlled trials are warranted to confirm these findings and evaluate the long-term cognitive benefits of GLP-1 RAs.”

References

1. Sun M, Wang X, Lu Z, et al. Evaluating GLP-1 receptor agonists versus metformin as first-line therapy for reducing dementia risk in type 2 diabetes. BMJ Open Diab Res Care 2025;13:e004902. doi:10.1136/ bmjdrc-2025-004902

2. Alzheimer’s Society. Diabetes and the risk of dementia. August 2024. Accessed July 22, 2025. https://www.alzheimers.org.uk/about-dementia/managing-the-risk-of-dementia/reduce-your-risk-of-dementia/diabetes

RAWALPINDI:

As part of Pakistan’s ongoing national immunisation programme to protect children from twelve life-threatening diseases, a new and critical initiative is being launched to vaccinate girls aged 9 to 15 against cervical cancer — a highly fatal yet preventable disease.

The vaccination campaign is set to begin in Rawalpindi on September 18, with the District Health Authority (DHA) already initiating the training of master trainers in preparation.

Cervical cancer, primarily caused by the Human Papillomavirus (HPV), carries a staggering mortality rate of 85%. Health experts emphasise that a single dose of the vaccine is sufficient to provide lasting immunity against the virus, offering a powerful defence against one of the most lethal forms of cancer affecting women globally.

Until now, Pakistan’s immunization efforts have focused on protecting children from twelve major diseases — tuberculosis, diphtheria, measles, whooping cough, tetanus, pneumonia, polio, diarrhoea, typhoid, TB, and hepatitis B. However, the rising number of cervical cancer cases, particularly among young girls, has raised alarm across public health circles. Pakistan now ranks seventh globally in cervical cancer prevalence.

Medical experts stress that early vaccination — between the ages of 9 and 15 — not only strengthens the immune response but also offers long-term protection before potential exposure to the virus.

According to Dr Ehsan Ghani, the Chief Executive Officer (CEO) of DHA Rawalpindi, the campaign will be rolled out in phases, beginning in Punjab and Sindh, and later expanding to Islamabad, Khyber-Pakhtunkhwa (K-P), and Balochistan.

To ensure smooth execution, training programmes for vaccination teams are already underway. Master trainers are being equipped with specialised knowledge, and a comprehensive micro-planning framework has been finalised.

Teams will function at three administrative levels — Union Council Medical Officers (UC MOs), Deputy District Health Officers (DDEHOs), and District Health Officers (DHOs) — to ensure coordinated implementation.

The initiative will be closely monitored by international partners, including UNICEF and the World Health Organisation (WHO), to uphold global standards of safety, efficiency, and effectiveness.

July 21, 2025 — Long COVID patients with abnormal cardiopulmonary PET/MR findings may be more likely to develop heart and lung diseases, according to new research published in the July issue of The Journal of Nuclear Medicine. The study — which included the largest cohort of long COVID subjects with cardiopulmonary symptoms with the longest follow-up duration — suggests that abnormal cardiopulmonary PET/MR should be considered a risk factor for future cardiac and pulmonary disease and that closer monitoring is warranted in these patients.

To date, the COVID pandemic has seen more than 400 million people infected worldwide, with more than 80 million infections and approximately one million deaths in the United States. Long COVID has emerged as a major public health challenge, affecting between one-third and two-thirds of patients many months after recovery from the initial COVID infection.

“Unfortunately, the long-term consequences of long COVID remain unknown,” said Maria Giovanna Trivieri, MD, PhD, FACC, FRCPC, associate professor of medicine (cardiology) and associate professor of radiology at the Icahn School of Medicine, Cardiovascular Research Institute, Biomedical and Molecular Imaging Institute, in New York, New York. “In this study we sought to use advanced cardiopulmonary imaging to assess for evidence of cardiac and lung abnormalities, vascular injury, and inflammation in patients with long COVID.”

The study included 98 patients with a history of COVID infection, persistent cardiopulmonary symptoms nine to 12 months after initial infection, and a clinical assessment compatible with long COVID. A control group that included subjects with a history of severe COVID but without cardiopulmonary symptoms at recruitment was also characterized. Both groups underwent cardiopulmonary 18F-FDG PET/MRI and dual-energy CT (DECT) of the lungs. A plasma protein analysis was also conducted for a subgroup of patients.

PET/MRI was abnormal for 57 percent of subjects, showing myocardial, pericardial, periannular, and vascular uptake, none of which was present on the PET/MR scans of the control group. Ninety percent of subjects presented abnormalities in DECT, including pulmonary infiltrates and abnormal perfusion. Analysis of plasma protein concentrations showed significant differences between the long COVID and the control groups, and the plasma protein profile was significantly different among long COVID patients with abnormal and normal PET/MR scans. During the four-year follow-up period, PET/MR abnormalities were more frequent in patients that subsequently developed heart failure, mitral regurgitation and pulmonary hypertension.

“The results of the study should raise awareness in the clinicians to elicit a proper history that includes prior COVID infection and long COVID symptoms,” stated Ana Devesa, MD, PhD, former postdoctoral fellow at Biomedical and Molecular Imaging Institute, in New York, and group leader at Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid, Spain. “If a temporal link is identified between symptoms and timing of infection, further evaluation might be appropriate. ”

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