Category: Neurology

Categories : Environmental Effects NeurologyTags :

Microplastics Rapidly Bioaccumulate Everywhere in the Body

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The prevalence of microplastics in the environment is well known, along with their harm to marine organisms, but few studies have examined the potential health impacts on mammals. Now, a new study published in the International Journal of Molecular Sciences has found that in mice, the infiltration of microplastics was as widespread in the body as it is in the environment, leading to behavioural changes, especially in older test subjects.

Study leader University of Rhode Island Professor Jaime Ross and her team focused on neurobehavioural effects and inflammatory response to exposure to microplastics, as well as the accumulation of microplastics in tissues, including the brain.

“Current research suggests that these microplastics are transported throughout the environment and can accumulate in human tissues; however, research on the health effects of microplastics, especially in mammals, is still very limited,” said Ross, an assistant professor of biomedical and pharmaceutical sciences at the Ryan Institute for Neuroscience and the College of Pharmacy. “This has led our group to explore the biological and cognitive consequences of exposure to microplastics.”

Behavioural changes detected

Ross’ team exposed young and old mice to varying levels of microplastics in drinking water over the course of three weeks. They found that microplastic exposure induces both behavioural changes and alterations in immune markers in liver and brain tissues. The study mice began to exhibit behaviours akin to dementia in humans. The results were even more profound in older animals.

“To us, this was striking. These were not high doses of microplastics, but in only a short period of time, we saw these changes,” Ross said. “Nobody really understands the life cycle of these microplastics in the body, so part of what we want to address is the question of what happens as you get older. Are you more susceptible to systemic inflammation from these microplastics as you age? Can your body get rid of them as easily? Do your cells respond differently to these toxins?”

To understand the physiological systems that may be contributing to these changes in behaviour, Ross’ team investigated how widespread the microplastic exposure was in the body, dissecting several major tissues including the brain, liver, kidney, gastrointestinal tract, heart, spleen and lungs. The researchers found that the particles had begun to bioaccumulate in every organ, including the brain, as well as in bodily waste.

“Given that in this study the microplastics were delivered orally via drinking water, detection in tissues such as the gastrointestinal tract, which is a major part of the digestive system, or in the liver and kidneys was always probable,” Ross said. “The detection of microplastics in tissues such as the heart and lungs, however, suggests that the microplastics are going beyond the digestive system and likely undergoing systemic circulation. The brain blood barrier is supposed to be very difficult to permeate. It is a protective mechanism against viruses and bacteria, yet these particles were able to get in there. It was actually deep in the brain tissue.”

Possible mechanism

That brain infiltration also may cause a decrease in glial fibrillary acidic protein (called “GFAP”), a protein that supports many cell processes in the brain, results have shown. “A decrease in GFAP has been associated with early stages of some neurodegenerative diseases, including mouse models of Alzheimer’s disease, as well as depression,” Ross said. “We were very surprised to see that the microplastics could induce altered GFAP signalling.”

She intends to investigate this finding further in future work. “We want to understand how plastics may change the ability for the brain to maintain its homeostasis or how exposure may lead to neurological disorders and diseases, such as Alzheimer’s disease,” she said.

Source: University of Rhode Island

Categories : NeurologyTags :

A Hidden Mathematical Rule Governs the Distribution of Neurons in the Brain

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Neuron densities in cortical areas in the mammalian brain follow a consistent distribution pattern. Image: Morales-Gregorio

Human Brain Project (HBP) researchers have uncovered how neuron densities are distributed across and within cortical areas in the mammalian brain. As reported in Cerebral Cortex, they have revealed a fundamental organisational principle of cortical cytoarchitecture: the ubiquitous lognormal distribution of neuron densities.

Numbers of neurons and their spatial arrangement play a crucial role in shaping the brain’s structure and function. Yet, despite the wealth of available cytoarchitectonic data, the statistical distributions of neuron densities remain largely undescribed. This new study from the HBP at Forschungszentrum Jülich and the University of Cologne (Germany) study advances our understanding of the organisation of mammalian brains.

The team accessed 9 publicly available datasets of seven species: mouse, marmoset, macaque, galago, owl monkey, baboon and human. After analysing the cortical areas of each, they found that neuron densities within these areas follow a consistent pattern – a lognormal distribution, pointing to a fundamental organisational principle underlying the densities of neurons in the mammalian brain.

A lognormal distribution is a statistical distribution characterised by a skewed bell-shaped curve. It arises, for instance, when taking the exponential of a normally distributed variable. It differs from a normal distribution in several ways. Most importantly, the curve of a normal distribution is symmetric, while the lognormal one is asymmetric with a heavy tail.

These findings are relevant for modelling the brain accurately. “Not least because the distribution of neuron densities influences the network connectivity,” says Sacha van Albada, leader of the Theoretical Neuroanatomy group at Forschungszentrum Jülich and senior author of the paper. “For instance, if the density of synapses is constant, regions with lower neuron density will receive more synapses per neuron,” she explains. Such aspects are also relevant for the design of brain-inspired technology such as neuromorphic hardware.

“Furthermore, as cortical areas are often distinguished on the basis of cytoarchitecture, knowing the distribution of neuron densities can be relevant for statistically assessing differences between areas and the locations of the borders between areas,” van Albada adds.

These results are in agreement with the observation that surprisingly many characteristics of the brain follow a lognormal distribution. “One reason why it may be very common in nature is because it emerges when taking the product of many independent variables,” says Alexander van Meegen, joint first author of the study. In other words, the lognormal distribution arises naturally as a result of multiplicative processes, similarly to how the normal distribution emerges when many independent variables are summed.

“Using a simple model, we were able to show how the multiplicative proliferation of neurons during development may lead to the observed neuron density distributions” explains van Meegen.

According to the study, in principle, cortex-wide organisational structures might be by-products of development or evolution that serve no computational function; but the fact that the same organisational structures can be observed for several species and across most cortical areas suggests that the lognormal distribution serves some purpose.

“We cannot be sure how the lognormal distribution of neuron densities will influence brain function, but it will likely be associated with high network heterogeneity, which may be computationally beneficial,” says Aitor Morales-Gregorio, first author of the study, citing previous works that suggest that heterogeneity in the brain’s connectivity may promote efficient information transmission. In addition, heterogeneous networks support robust learning and enhance the memory capacity of neural circuits.

Source: Human Brain Project

Categories : Ageing NeurologyTags :

Social Isolation Linked to Reduced Brain Volume in Older People

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A study of nearly 9000 older people in Japan found that those who have little social contact with others may be more likely to have reduction of overall brain volume, and in areas of the brain affected by dementia, compared with those who have more frequent social contact. The study results were published in Neurology.

“Social isolation is a growing problem for older adults,” said study author Toshiharu Ninomiya, MD, PhD, of Kyushu University in Fukuoka, Japan. “These results suggest that providing support for people to help them start and maintain their connections to others may be beneficial for preventing brain atrophy and the development of dementia.”

The study involved 8896 people without dementia, average age 73. They had MRI brain scans and health exams, and were asked how often they were in contact with friends or relatives that did not live with them.

The people with the lowest amount of social contact had overall brain volume that was significantly lower than those with the most social contact. The total brain volume, or the sum of white and grey matter, as a percentage of the total intracranial volume, or the volume within the cranium, including the brain, meninges, and cerebrospinal fluid, was 67.3% in the lowest contact group compared to 67.8% in the highest contact group. They also had lower volumes in areas of the brain such as the hippocampus and amygdala that play a role in memory and are affected by dementia.

The researchers took into account other factors that could affect brain volume, such as age, diabetes, smoking and exercise.

The socially isolated people also had more small areas of damage in the brain, called white matter lesions, than the people with frequent social contact. The percentage of intracranial volume made up of white matter lesions was 0.30 for the socially isolated group, compared to 0.26 for the most socially connected group.

The researchers found that symptoms of depression partly explained the relationship between social isolation and brain volumes. However, symptoms of depression accounted for only 15% to 29% of the association.

“While this study is a snapshot in time and does not determine that social isolation causes brain atrophy, some studies have shown that exposing older people to socially stimulating groups stopped or even reversed declines in brain volume and improved thinking and memory skills, so it’s possible that interventions to improve people’s social isolation could prevent brain volume loss and the dementia that often follows,” Ninomiya said.

Since the study involved only older Japanese people, a limitation is that the findings may not be generalisable to people of other ethnicities and younger people.

Source: American Academy of Neurology

Categories : Metabolic Disorders NeurologyTags :

Liraglutide Boosts Associative Learning in People with Obesity

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Obesity leads to altered energy metabolism and reduced insulin sensitivity of cells. The so-called “anti-obesity drugs” such as liraglutide are increasingly used to treat obesity and have caused tremendous interest, especially in the USA. Researchers in Germany have now shown in people with obesity that reduced insulin sensitivity affects learning of sensory associations. The results, published in Nature Metabolism, showed that a single dose of liraglutide was able to normalise these changes and restore the underlying brain circuit function.

The brain must be able to form associations in order to control behaviour. This involves, for example, associating a neutral external stimulus with a consequence following the stimulus. In this way, the brain learns what the implication of handling of the first stimulus are. Associative learning is the basis for forming neural connections and gives stimuli their motivational force. It is essentially controlled by a brain region called the dopaminergic midbrain. This region has many receptors for the body’s signalling molecules, such as insulin, and can thus adapt behaviour to the body’s physiological needs.

But what happens when the body’s insulin sensitivity is reduced due to obesity? Does this change brain activity, ability to learn associations and thus behaviour? Researchers at the Max Planck Institute for Metabolism Research have now measured how well the learning of associations works in participants with normal body weight (high insulin sensitivity, 30 volunteers) and in participants with obesity (reduced insulin sensitivity, 24 volunteers), and if this learning process is influenced by the anti-obesity drug liraglutide.

Low insulin sensitivity reduces the brain’s ability to associate sensory stimuli.

In the evening, they injected the participants with either the drug liraglutide or a placebo in the evening. Liraglutide is a so-called GLP-1 agonist, which activates the GLP-1 receptor in the body, stimulating insulin production and producing a feeling of satiety. It is often used to treat obesity and type 2 diabetes and is given once a day. The next morning, the subjects were given a learning task that allowed the researchers to measure how well associative learning works. They found that the ability to associate sensory stimuli was less pronounced in participants with obesity than in those of normal weight, and that brain activity was reduced in the areas encoding this learning behaviour.

After just one dose of liraglutide, participants with obesity no longer showed these impairments, and no difference in brain activity was seen between participants with normal weight and obesity. In other words, the drug returned the brain activity to the state of normal-weight subjects.

“These findings are of fundamental importance. We show here that basic behaviours such as associative learning depend not only on external environmental conditions but also on the body’s metabolic state. So, whether someone has overweight or not also determines how the brain learns to associate sensory signals and what motivation is generated. The normalisation we achieved with the drug in subjects with obesity, therefore, fits with studies showing that these drugs restore a normal feeling of satiety, causing people to eat less and therefore lose weight,” says study leader Marc Tittgemeyer from the Max Planck Institute for Metabolism Research.

“While it is encouraging that available drugs have a positive effect on brain activity in obesity, it is alarming that changes in brain performance occur even in young people with obesity without other medical conditions. Obesity prevention should play a much greater role in our healthcare system in the future. Lifelong medication is the less preferred option in comparison primary prevention of obesity and associated complications,” says Ruth Hanßen, first author of the study and a physician at the University Hospital of Cologne.

Source: Max Planck Institute for Biology of Ageing

Categories : Neurology Regenerative MedicineTags :

New Regeneration Drug for Spinal Cord Injury Passes Safety Check

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Researchers in the UK have evaluated a potential drug for the treatment of spinal cord injury (SCI), which could potentially regrow damaged nerves, and found it to be safe and tolerable. The results of their Phase 1 clinical trial were published in British Journal of Clinical Pharmacology and evaluated the KCL-286 drug, which activates retinoic acid receptor beta (RARb) in the spine to promote recovery.

There are no licensed drugs that can fix the adult central nervous system’s inability to regenerate. Implants have been able to restore some function, but for most, spinal cord injuries are life-changing.

Previous studies have shown that nerve growth can be stimulated by activating the RARb2 receptor, but no drug suitable for humans has been developed. KCL-286, an RARb2 agonist, was developed by Professor Corcoran and team and used in a first in man study to test its safety in humans.

The study by the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, recruited 109 healthy males in a single ascending dose (SAD) adaptive design with a food interaction (FI) arm, and multiple ascending dose (MAD) arm. Participants in each arm were further divided into different dose treatments.

SAD studies are designed to establish the safe dosage range of a medicine by providing participants with small doses before gradually increasing the dose provided. Researchers look for any side effects, and measure how the medicine is processed within the body. MAD studies explore how the body interacts with repeated administration of the drug, and investigate the potential for a drug to accumulate within the body.

Researchers found that participants were able to safely take 100mg doses of KCL-286, with no severe adverse events.

Professor Jonathan Corcoran, Professor of Neuroscience and Director of the Neuroscience Drug Discovery Unit, at King’s IoPPN and the study’s senior author said, “This represents an important first step in demonstrating the viability of KCL-286 in treating spinal cord injuries. This first-in-human study has shown that a 100mg dose delivered via a pill can be safely taken by humans. Furthermore, we have also shown evidence that it engages with the correct receptor.

“Our focus can hopefully now turn to researching the effects of this intervention in people with spinal cord injuries.”

Dr Bia Goncalves, a senior scientist and project manager of the study, and the study’s first author from King’s IoPPN said, “Spinal Cord Injuries are a life changing condition that can have a huge impact on a person’s ability to carry out the most basic of tasks, and the knock-on effects on their physical and mental health are significant.

“The outcomes of this study demonstrate the potential for therapeutic interventions for SCI, and I am hopeful for what our future research will find.”

The researchers are now seeking funding for a Phase 2a trial studying the safety and tolerability of the drug in those with SCI.

Source: King’s College London

Categories : NeurologyTags :

Source of Hidden Consciousness in ‘Comatose’ Brain Injury Patients Found

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Researchers have identified brain injuries that may underlie hidden consciousness, a puzzling phenomenon in which brain-injured patients are unable to respond to simple commands, making them appear unconscious despite having some level of awareness.

“Our study suggests that patients with hidden consciousness can hear and comprehend verbal commands, but they cannot carry out those commands because of injuries in brain circuits that relay instructions from the brain to the muscles,” says study leader Jan Claassen, MD, associate professor of neurology at Columbia University.

The findings, published in the journal Brain, could help physicians more quickly identify brain-injured patients who might have hidden consciousness and better predict which patients are likely to recover with rehabilitation.

Brain circuits disrupted in patients with hidden consciousness

Hidden consciousness, also known as cognitive motor dissociation (CMD), occurs in 15–25% of patients with brain injuries stemming from head trauma, brain haemorrhage, or cardiac arrest.

In previous research, Claassen and colleagues found that subtle brainwaves detectable with EEG are the strongest predictor of hidden consciousness and eventual recovery for unresponsive brain-injured patients.

But the precise pathways in the brain that become disrupted in this condition were unknown.

In the new study, the researchers used EEG to examine 107 brain injury patients. The technique can determine when patients are trying, though unable, to respond to a command such as “keep opening and closing your right hand.”

The analysis detected CMD in 21 of the patients. The researchers then analysed structural MRI scans from all of the patients.

“Using a technique we developed called bi-clustering analysis, we were able to identify patterns of brain injury that are shared among patients with CMD and contrast to those without CMD,” says co-lead author Qi Shen, PhD, associate research scientist in the Claassen lab.

The researchers found that all of the CMD patients had intact brain structures related to arousal and command comprehension, supporting the notion that these patients were hearing and understanding the commands but were unable to carry them out.

“We saw that all of the CMD patients had deficits in brain regions responsible for integrating comprehended motor commands with motor output, preventing CMD patients from acting on verbal commands,” says Claassen.

The findings may allow researchers to better understand which brain injury patients have CMD, which will be useful for clinical trials that support recovery of consciousness.

More research is required before these approaches can be applied to clinical practice. “However, our study shows that it may be possible to screen for hidden consciousness using widely available structural brain imaging, moving the detection of CMD one step closer to general clinical use,” Claassen says.

“Not every critical care unit may have resources and staff that is trained in using EEG to detect hidden consciousness, so MRI may offer a simple way to identify patients who require further screening and diagnosis.”

Source: Columbia University Irving Medical Center

Categories : Implants and Prostheses NeurologyTags :

For Stroke Recovery, Deep Brain Stimulation may Aid Rehabilitation

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Deep brain stimulation illustration. Credit: NIH

A first-in-human trial of deep brain stimulation (DBS) for post-stroke rehabilitation patients has shown that using DBS to target the dentate nucleus – which regulates fine-control of voluntary movements, cognition, language, and sensory functions in the brain – is safe and feasible.

The EDEN trial (Electrical Stimulation of the Dentate Nucleus for Upper Extremity Hemiparesis Due to Ischemic Stroke) also shows that the majority of participants (9 of 12) demonstrated improvements in both motor impairment and function. Importantly, the study found that participants with at least minimal preservation of distal motor function at enrolment showed gains that almost tripled their initial scores.

Published in Nature Medicine, these findings build on more than a decade of preclinical work led by principal investigators Andre Machado, MD, PhD, and Kenneth Baker, PhD, at Cleveland Clinic.

“These are reassuring for patients as the participants in the study had been disabled for more than a year and, in some cases, three years after stroke. This gives us a potential opportunity for much needed improvements in rehabilitation in the chronic phases of stroke recovery,” said Dr Machado, patented the DBS method in stroke recovery. “The quality-of-life implications for study participants who responded to therapy have been significant.”

“We saw patients in the study regain levels of function and independence they did not have before enrolling in the research,” Dr Machado said. “This was a smaller study and we look forward to expanding as we have begun the next phase.”

The completed EDEN trial enrolled 12 individuals with chronic, moderate-to-severe hemiparesis of the upper extremity as a result of a unilateral middle cerebral artery stroke 12-to-36 months prior. There were no major complications throughout the study. Nine of the 12 participants improved to a degree that is considered meaningful in stroke rehabilitation.

Source: Cleveland Clinic

Categories : Cancer NeurologyTags :

In A First, Immunotherapy for Glioblastoma Successfully Tested in Mice

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Immunotherapy has dramatically improved survival against many cancers but efforts to use it against glioblastomas have to date proven fruitless. Now, Salk scientists have found the immunotherapy treatment anti-CTLA-4 leads to considerably greater survival of mice with glioblastoma. Furthermore, they discovered that this therapy was dependent on immune cells called CD4+ T cells infiltrating the brain and triggering the tumour-destructive activities of other immune cells called microglia, which permanently reside in the brain.

The findings, published in the journal Immunity, show the benefit of harnessing the body’s own immune cells to fight brain cancer and could lead to more effective immunotherapies for treating brain cancer in humans.

Glioblastoma, the most common and deadly form of brain cancer, grows rapidly to invade and destroy healthy brain tissue. The tumour sends out cancerous tendrils into the brain that make surgical tumour removal extremely difficult or impossible.

“There are currently no effective treatments for glioblastoma – a diagnosis today is basically a death sentence,” says Professor Susan Kaech, senior author and director of the NOMIS Center for Immunobiology and Microbial Pathogenesis. “We’re extremely excited to find an immunotherapy regimen that uses the mouse’s own immune cells to fight the brain cancer and leads to considerable shrinkage, and in some cases elimination, of the tumour.”

For some tumours, immunotherapy can be used, in which the body’s own immune cells to seek and destroy cancer cells, leading to strong, lasting anti-cancer responses for many patients. Kaech sought new ways of harnessing the immune system to develop more safe and durable treatments for brain cancer.

Her team found three cancer-fighting tools that have been somewhat overlooked in brain cancer research that may cooperate and effectively attack glioblastoma: an immunotherapy drug called anti-CTLA-4 and specialized immune cells called CD4+ T cells and microglia.

Anti-CTLA-4 immunotherapy works by blocking cells from making the CTLA-4 protein, which, if not blocked, inhibits T cell activity. It was the first immunotherapy drug designed to stimulate our immune system to fight cancer, but it was quickly followed by another, anti-PD-1, that was less toxic and became more widely used. Whether anti-CTLA-4 is an effective treatment for glioblastoma remains unknown since anti-PD-1 took precedence in clinical trials. Unfortunately, anti-PD-1 was found to be ineffective in multiple clinical trials for glioblastoma – a failure that inspired Kaech to see whether anti-CTLA-4 would be any different.

As for the specialized immune cells, CD4+ T cells are often overlooked in cancer research in favour of a similar immune cell, the CD8+ T cell, because CD8+ T cells are known to directly kill cancer cells. Microglia live in the brain full time, where they patrol for invaders and respond to damage – whether they play any role in tumour death was not clear. When treated with anti-CLA-4, mice with glioblastoma had longer lifespans than those receiving anti-PD-1.

Upon investigation, they found that after anti-CTLA-4 treatment, CD4+ T cells secreted a protein called interferon gamma that caused the tumour to throw up “stress flags” while simultaneously alerting microglia to start eating up those stressed tumour cells. As they gobbled up the tumour cells, the microglia would present scraps of tumour on their surface to keep the CD4+ T cells attentive and producing more interferon gamma, creating a cycle that lasts until the tumour is destroyed.

“Our study demonstrates the promise of anti-CTLA-4 and outlines a novel process where CD4+ T cells and other brain-resident immune cells team up to kill cancerous cells,” says co-first author Dan Chen, a postdoctoral researcher in Kaech’s lab.

To understand the role of microglia in this cycle, the researchers collaborated with co-author and Salk Professor Greg Lemke. For decades, Lemke has investigated critical molecules, called TAM receptors, used by microglia to send and receive crucial messages. The researchers found that TAM receptors told microglia to gobble up cancer cells in this novel cycle.

“We were stunned by this novel codependency between microglia and CD4+ T cells,” says co-first author Siva Karthik Varanasi, a postdoctoral researcher in Kaech’s lab. “We are already excited about so many new biological questions and therapeutic solutions that could radically change treatment for deadly cancers like glioblastoma.”

Connecting the pieces of this cancer-killing puzzle brings researchers closer than ever to understanding and treating glioblastoma.

“We can now reimagine glioblastoma treatment by trying to turn the local microglia that surround brain tumours into tumour killers,” says Kaech. “Developing a partnership between CD4+ T cells and microglia is creating a new type of productive immune response that we have not previously known about.”

Next, the researchers will examine whether this cancer-killing cell cycle is present in human glioblastoma cases. Additionally, they aim to look at other animal models with differing glioblastoma subtypes, expanding their understanding of the disease and optimal treatments.

Source: Salk Institute

Categories : NeurologyTags :

Study Resolves Long-standing Question on Gating of Ion Channels

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Source: CC0

Ion channels play a crucial role in many cellular processes, including neuronal communication, muscle contraction or cell proliferation. Most multi subunit ion channels exist in two functional states, either closed or open. During gating, one should expect that all subunits undergo conformational changes – but there are no intermediate conduction levels. To find out why, researchers from the University of Vienna and the Washington University in St. Louis created a smart model system. The study is currently published in Nature Communications.

Ion channels are membrane proteins that regulate the electrical activity of cells. In this study the scientific team investigated the inwardly rectifying potassium channel Kir2. This channel is crucial for maintaining a negative membrane potential in many cells. These channels are promising drug targets for treatment of cardiovascular diseases. To foster drug development, a detailed understanding of the gating mechanism is important.

Intelligent model system & innovative methods

“We designed a model system that allowed us to visualise the gating of individual subunits and track conductance changes,” explains Grigory Maksaev from the Washington University in St. Louis. As a model system, the inwardly rectifying potassium channel Kir2 was used. This channel is crucial for maintaining a negative membrane potential in many cells. “We introduced an acidic residue near the channel gate. This led to novel states, so-called sub-conductance states” explains Eva Plessl from the Department of Pharmaceutical Sciences, University of Vienna. The life times of these sub-states were long enough to resolve them experimentally. Each of the observed sub-states represents a distinct subunit conformation. Interestingly, the sub-state occupancy is titratable by pH. “This suggests that protonation or deprotonation of individual acidic residues causes this phenomenon,” explains Sun-Joo Lee from the Washington University in St. Louis.

Sour is…less conductive

“Molecular dynamics simulations with different protonation states of the acidic residue support this finding,” explains Anna Weinzinger from the Department of Pharmaceutical Sciences, University of Vienna. The study reveals that each subunit gating transition leads to conductance level changes. This suggests that for a fully open channel, all subunits must move together. “By designing a smart model system, we have answered a long-standing question about ion channel gating,” explains Colin Nichols from the Washington University in St. Louis.

Source: University of Vienna

Categories : Gastrointestinal NeurologyTags :

Possible Dementia Risk from Long Term Proton Pump Inhibitor Use

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Source: Pixabay CC0

People who take proton pump inhibitors for acid reflux four-and-a-half years or more may have a higher risk of dementia compared to people who do not take these medications, according to new research published in Neurology.

Acid reflux is when stomach acid flows into the oesophagus, usually after a meal or when lying down, resulting in heartburn and ulcers. People with frequent acid reflux may develop gastroesophageal reflux disease, or GERD, which can lead to cancer of the oesophagus. Proton pump inhibitors reduce stomach acid by targeting the enzymes in the stomach lining that produce that acid.

“Proton pump inhibitors are a useful tool to help control acid reflux, however long-term use has been linked in previous studies to a higher risk of stroke, bone fractures and chronic kidney disease,” said study author Kamakshi Lakshminarayan, MBBS, PhD, of the University of Minnesota School of Public Health in Minneapolis, and a member of the American Academy of Neurology. “Still, some people take these drugs regularly, so we examined if they are linked to a higher risk of dementia. While we did not find a link with short-term use, we did find a higher risk of dementia associated with long-term use of these drugs.”

The study included 5712 people, aged 45 and up, without dementia at the start of the study. They had an average age of 75.

Researchers determined if participants took acid reflux drugs by reviewing their medications during study visits and during yearly phone calls. Of the participants, 1490 people, or 26%, had taken the drugs. Participants were then divided into four groups based on whether they had taken the drugs and for how long, as follows: people who did not take the drugs; those who took the drugs for up to 2.8 years; those who took them for 2.8 to 4.4 years; and people who took them for more than 4.4 years.

Participants were then followed for a median duration of 5.5 years. During this time, 585 people, or 10%, developed dementia.

Of the 4222 people who did not take the drugs, 415 people developed dementia, or 19 cases per 1000 person-years. Person-years represent both the number of people in the study and the amount of time each person spends in the study. Of the 497 people who took the drugs for more than 4.4 years, 58 people developed dementia, or 24 cases per 1000 person-years.

After adjusting for factors such as age, sex and race, as well as health-related factors such as high blood pressure and diabetes, researchers found people who had been taking acid reflux drugs for more than 4.4 years had a 33% higher risk of developing dementia than people who never took the drugs.

Researchers did not find a higher risk of dementia for people who took the drugs for fewer than 4.4 years.

“More research is needed to confirm our findings and explore reasons for the possible link between long-term proton pump inhibitor use and a higher risk of dementia,” said Lakshminarayan. “While there are various ways to treat acid reflux, such as taking antacids, maintaining a healthy weight, and avoiding late meals and certain foods, different approaches may not work for everyone. It is important that people taking these medications speak with their doctor before making any changes, to discuss the best treatment for them, and because stopping these drugs abruptly may result in worse symptoms.”

A limitation of the study was that participants were asked once a year about medication use, so researchers estimated use between annual check-ins. If participants stopped and restarted acid reflux drugs in between check-ins, estimation of their use may have been inaccurate. The authors were also unable to assess if participants took over the counter acid reflux drugs.

Source: American Academy of Neurology