Category: Neurology

Categories : Ageing NeurologyTags :

Quitting Smoking Late in Life May Still Slow Cognitive Decline

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Photo by Sara Kurfess on Unsplash

Quitting smoking in middle age or later is linked to slower age-related cognitive decline over the long term, according to a new study by UCL researchers.

The study, published in The Lancet Healthy Longevity, looked at data from 9436 people aged 40 or over (average age: 58) in 12 countries, comparing cognitive test results among people who quit smoking with those of a matched control group who kept smoking.

The research team found that the cognitive scores of those who had quit smoking declined significantly less than their smoking counterparts in the six years after they quit. For verbal fluency, the rate of decline roughly halved, while for memory it slowed by 20%.

Since slower cognitive decline is related to reduced dementia risk, their findings add to a growing body of evidence suggesting quitting smoking might be a preventative strategy for the disease. Still, more research is needed to confirm this.

Lead author Dr Mikaela Bloomberg (UCL Institute of Epidemiology & Health Care) said: “Our study suggests that quitting smoking may help people to maintain better cognitive health over the long term even when we are in our 50s or older when we quit.

“We already know that quitting smoking, even later in life, is often followed by improvements in physical health and well-being. It seems that, for our cognitive health too, it is never too late to quit.

“This finding is especially important because middle-aged and older smokers are less likely to try to quit than younger groups, yet they disproportionately experience the harms of smoking. Evidence that quitting may support cognitive health could offer new compelling motivation for this group to try and quit smoking.

“Also, as policymakers wrestle with the challenges of an ageing population, these findings provide another reason to invest in tobacco control.”

Smoking is thought to harm brain health in part because it affects cardiovascular health – smoking causes damage to blood vessels that supply oxygen to the brain. Smoking is also thought to affect cognitive health by causing chronic inflammation and directly damaging brain cells through oxidative stress (due to the creation of unstable molecules called free radicals).

Co-author Professor Andrew Steptoe (UCL Institute of Epidemiology & Health Care) said: “Slower cognitive decline is linked to lower dementia risk. These findings add to evidence suggesting that quitting smoking might be a preventative strategy for the disease. However, further research will be needed that specifically examines dementia to confirm this.”

Previous studies, the researchers noted, had found a short-term improvement in cognitive function after people stopped smoking. But whether this improvement was sustained over the longer term – particularly when people quit smoking later in life – was not known.

To answer this question the research team looked at data from three ongoing studies* where a nationally representative group of participants answered survey questions every two years. The studies covered England, the US, and 10 other European countries.

More than 4,700 participants who quit smoking were compared with an equal number of people who carried on smoking. The two groups were matched in terms of their initial cognitive scores and other factors such as age, sex, education level, and country of birth.

The research team found that the two groups’ scores in memory and verbal fluency tests declined at a similar rate in the six years prior to participants of one group quitting smoking. These trajectories then diverged in the six years following smoking cessation.

For the smokers who quit, the rate of decline was about 20% slower for memory and 50% slower for verbal fluency. In practical terms, this meant that with each year of ageing, people who quit experienced three to four months less memory decline and six months less fluency decline than those who continued smoking.

This was an observational analysis, so unmeasured differences between smokers who quit and continuing smokers could remain; while the trends before quitting were similar, the study cannot prove cause and effect.

However, the research team noted their findings were consistent with earlier studies showing that adults aged over 65 who quit smoking during early- or mid-life have comparable cognitive scores to never smokers, and that former and never smokers have a similar risk of dementia a decade or longer after quitting.

*The longitudinal studies were the English Longitudinal Study of Ageing (ELSA), the Survey of Health, Ageing and Retirement in Europe (SHARE), and the Health and Retirement Study (HRS).

Source: University College London

Categories : Ageing Diet and Nutrition NeurologyTags :

Link Between Calcium Supplements and Dementia Debunked by New Research

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New research has found no evidence that calcium monotherapy increases the long-term risk for dementia.

Photo by cottonbro studio

New research from Edith Cowan University (ECU), Curtin University and the University of Western Australia has found no evidence that calcium monotherapy increases the long-term risk for dementia, helping to dispel previous concerns about its potential negative effects on brain health in older women.

This study, which leveraged outcomes from prior research that provided calcium supplements or a placebo to 1460 older women over a five-year period, found that the supplement did not increase the long-term risk of dementia.

“Calcium supplements are often recommended to prevent or manage osteoporosis,” said ECU PhD student Ms Negar Ghasemifard.

Around 20 per cent of women over the age of 70 are affected by osteoporosis and calcium supplementation is widely recommended as a preventative measure against fracture.

“Previous research has raised concerns around the impacts that calcium supplements could have on cognitive health, particularly dementia. Results from our study provides reassurance to patients and clinicians regarding the safety of calcium supplements in the context of dementia risk for older women,” Ms Ghasemifard said.

ECU Senior Research Fellow Dr Marc Sim noted that when the analysis was adjusted for supplement compliance, a range of lifestyle factors, including dietary calcium intake and genetic risk, the results remained unchanged.

“Previous research suggesting potential links between calcium supplement use and the risk for dementia was purely observational in nature. Our research, in comparison, consisted of a post-hoc analysis from a 5-year double-blind, placebo controlled randomised clinical trial on calcium supplements to prevent fracture. Whilst our study is still epidemiology, its design does reduce the likelihood of unmeasured confounding”

“Some 730 older women were given calcium supplements over five years, and a further 730 were given placebo. This study design offers more accurate data on dosage and duration, and we had a long follow-up period of 14.5 years, which strengthens our results,” Dr Sim said.

While these findings may alleviate concerns regarding calcium supplementation and all-cause dementia risk in older women, particularly after the age of 80 years, Professor Simon Laws, Director of ECU’s Centre for Precision Health, said further research was required.

“Whether this extrapolates to other demographics, such as men or even women commencing supplementation earlier in life, remains unknown. To confirm the current findings, particularly regarding brain health, and to address these population gaps, future clinical trials of calcium supplements, with or without vitamin D, would need to be undertaken. These should include specific and robust assessments of brain health as the primary outcome measures.”

Curtin University’s Professor Blossom Stephan, Director of the Dementia Centre of Excellence and a Dementia Australia Honorary Medical Advisor said the research highlighted a very important finding that provides reassurance to clinicians and patients about the long-term safety of calcium supplementation.

“Given calcium’s critical role in multiple physiological functions, including bone health, these results provide reassurance that long-term calcium supplementation did not increase dementia risk in older women,” she said.

Source: Edith Cowan University

Categories : Cancer NeurologyTags :

New Research Shows that Cancer Can Damage the Myelin Sheath

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Myelin sheath damage. Credit: Scientific Animations CC4.0

A new study, published in Nature, underscores the importance of investigating interactions between cancer and the nervous system – a field known as cancer neuroscience. The results suggest that targeting the signalling pathways involved can reverse this inflammation and improve treatment responses.

“These findings uncover novel mechanisms by which the immune system and nerves within the tumour microenvironment interact, revealing actionable targets that could transform the way we approach resistance to immunotherapy in patients with cancer,” said co-corresponding author Moran Amit, MD, PhD, professor of Head and Neck Surgery. “This marks a significant advance in our understanding of tumour-neuro-immune dynamics, highlighting the importance of investigating the interplay of cancer and neuroscience in meaningful ways that can directly impact clinical practice.”

Tumours can sometimes infiltrate the space around nerves and nervous system fibres that are in close proximity, a process known as perineural invasion, which leads to poor prognosis and treatment escalation in various cancer types. Yet little is known about how this invasion affects or interacts with the immune system.

The study, co-led by Amit, Neil Gross, MD, professor of Head and Neck Surgery, and Jing Wang, PhD, professor of Bioinformatics and Computational Biology, examined the role of perineural invasion and cancer-associated nerve injury in relation to the development of immunotherapy resistance commonly seen in patients with squamous cell carcinoma, melanoma and stomach cancer.

Collaborating with the immunotherapy platform, part of the James P. Allison Institute, the team analysed trial samples using advanced genetic, bioinformatic and spatial techniques. The researchers revealed that cancer cells break down the protective myelin sheaths that cover nerve fibres, and that the injured nerves promote their own healing and regeneration through an inflammatory response.

Unfortunately, this inflammatory response gets caught in a chronic feedback loop as tumors continue to grow, repeatedly damaging nerves which then recruit and exhaust the immune system, ushering in an immunosuppressive tumor microenvironment that leads to treatment resistance. The study showed that targeting the cancer-induced nerve injury pathway at different points can reverse this resistance and improve treatment response.

Importantly, the authors point out that this reduced neuronal health is directly associated with perineural invasion and cancer-induced nerve injury, rather than a general cancer-induced effect, highlighting the importance of studying cancer-nerve interactions that can potentially contribute to cancer progression.

As part of MD Anderson’s Cancer Neuroscience Program, researchers are investigating scientific themes – such as neurobiology, tumours of the brain and spine, neurotoxicities and neurobehavioural health – to understand how the nervous system and cancer interact and how this affects patients throughout their cancer journey.

Source: University of Texas MD Anderson Cancer Center

Categories : NeurologyTags :

Disconnected Hemisphere in Epilepsy Patients Lingers in a Sleep-like State

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Surgically isolated, seizure-causing neural tissue shows evidence suggestive of absent or reduced awareness

This metaphorical illustration reimagines a hidden view of the brain of a patient with hemispherotomy. In the absence of subcortical activating inputs, the disconnected cortex defaults to a sleep-like state, marked by slow-wave EEG activity and evocatively represented here as night. By contrast, the intact hemisphere, still integrated with subcortical structures, sustains wakefulness and a bright inner world capable of environmental interaction, reflected in faster EEG rhythms. The image underscores the divergence of cortical states after hemispheric isolation.
Image credit: Michele A. Colombo (CC-BY 4.0)

Sleep-like slow-wave patterns persist for years in surgically disconnected neural tissue of awake epilepsy patients, according to a study published October 16th in the open-access journal PLOS Biology by Marcello Massimini from Universita degli Studi di Milano, Italy, and colleagues. The presence of slow waves in the isolated hemisphere impairs consciousness, however, whether they serve any functional or plastic role, remains unclear.

Hemispherotomy is a surgical procedure used to treat severe cases of epilepsy in children. The goal of this procedure is to achieve maximal disconnection of the diseased neural tissue, potentially encompassing an entire hemisphere, from the rest of the brain to prevent the spread of seizures. The disconnected cortex – the outer layer of neural tissue in the brain – is not surgically removed and has a preserved vascular supply. Because it is isolated from sensory and motor pathways, it cannot be evaluated behaviourally, leaving open the question of whether it retains internal states consistent with some form of awareness. More broadly, the activity patterns that large portions of the disconnected cortex can sustain in awake humans remain poorly understood.

To address these questions, Massimini and colleagues used electroencephalography (EEG) to measure activity in the isolated cortex during wakefulness before and up to three years after surgery in 10 paediatric patients, focusing on non-epileptic background activity. Following surgery, prominent slow waves appeared over the disconnected cortex. This is novel evidence that this pattern can last for months and years after complete cortical disconnection. The persistence of slow waves raises the question of whether they play any functional role or merely reflect a regression to a default mode of cortical activity.

The pronounced broad-band EEG slowing resembled patterns observed in conditions such as deep non-rapid eye movement (NREM) sleep, general anaesthesia, and the vegetative state. The findings indicate absent or reduced likelihood of dream-like experiences in the isolated cortex. Overall, the EEG evidence is compatible with a state of absent or reduced awareness.

According to the authors, any inference about the presence or absence of consciousness, based solely on the brain’s physical properties such as prominent EEG slow waves, should be approached with caution, particularly in neural structures that are not behaviourally accessible. The slowing observed at the scalp level should be further characterised with intracranial recordings in cases in which clinical outcomes require postoperative invasive monitoring.

Michele A. Colombo says, “This is only the beginning of shedding light on the problem of consciousness in inaccessible systems. During the revision process, we were confronted with different perspectives, revealing the complexity of this problem.”

Marcello Massimini adds, “This pattern may provide clues to why sleep-like brain activity emerges in patients with brain lesions, and how it relates to their level of awareness.”

Anil K. Seth adds, “This has been an exciting and deeply satisfying scientific journey. It started years ago with philosophical discussions about the possibility of ‘islands of awareness’ in completely isolated neural systems, to, now, this wonderful collaboration which has shed important experimental light on this clinically important issue.”

Tim Bayne finally states, “The study of consciousness involves many puzzling cases in which it is unclear what to say about the possibility of subjective experience. As a philosopher, it’s been deeply rewarding to explore a new frontier in consciousness science with this wonderful team of scientists and clinicians.” 

Provided by PLOS

Categories : Neurology PaediatricsTags :

The Power of Touch: Skin-to-skin Contact Linked to Preemie Brain Growth

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Photo by Hush Naidoo on Unsplash

Preterm infants born before 32 weeks who received more skin-to-skin contact while in the hospital showed stronger brain development in areas tied to emotion and stress regulation than babies who received less skin-to-skin care, according to a study published in Neurology®, the medical journal of the American Academy of Neurology. The study can only show an association and cannot establish causation.

“Skin-to-skin contact in preterm infants has been shown to have many benefits, with previous studies linking it to improved bonding, sleep, heart and lung function and growth, as well as reduced pain and stress,” said study author Katherine E. Travis, PhD, of Burke Neurological Institute in White Plains, New York. “Our findings in infants born very preterm suggest skin-to-skin care may also play a role in shaping early brain development, highlighting the potential importance of caregiving experiences during the earliest weeks of a preemie’s life.”

he study included 88 preterm infants with an average gestational age of 29 weeks who weighed an average of 2.65 pounds. The average stay in the hospital was two months. The goal was to find out whether skin-to-skin holding, also called kangaroo care, was linked to brain development in areas that help regulate emotions and stress. Researchers tracked skin-to-skin care with family members throughout each infant’s hospitalisation, including how long each session lasted and the total minutes per day. Families visited an average of once per day. When they provided skin-to-skin care, the average session was around 70 minutes with 73% of sessions provided by mothers. For the entire hospital stay, the average amount of skin-to-skin care per day was 24 minutes.

Each infant received a brain scan before going home from the hospital – around the time they would have reached full-term age of around 40 weeks. The brain scans measured how water moves through brain tissue. This movement helps reveal how white matter – the brain’s communication network – is developing. Researchers then compared the markers of white matter with the amount of time the preemies received skin-to-skin care per session and per day.

For skin-to-skin duration per session, researchers found longer sessions were linked to higher mean diffusivity – how freely water moves through the brain – in two key brain regions: the cingulum, which supports attention and emotion regulation; and the anterior thalamic radiations, which connects areas involved in emotional processing and memory.

Longer sessions were also linked to lower fractional anisotropy – how water movement is influenced by developing cellular tissues – in the anterior thalamic radiations. For daily total minutes of skin-to-skin care, researchers found higher amounts were linked to higher mean diffusivity in the anterior thalamic radiations. They were also linked to lower fractional anisotropy in the anterior thalamic radiations. These associations remained significant even after researchers accounted for factors that could influence brain development, including gestational age at birth, age at time of scan, socioeconomic status and how often family visited.

“Our findings add to growing evidence that white matter development is sensitive to a preterm infant’s experience while in the hospital,” said Travis. “Skin-to-skin care not only provides preterm infants with family connections through bonding, it may also be encouraging new connections within the brain itself, improving a baby’s brain health overall.”

A limitation of the study is that it was conducted at a single hospital and researchers reviewed existing medical records. The authors note that future research should explore how early caregiving experiences – like skin-to-skin care – might shape brain development and support later behavioural outcomes as preterm infants grow.

Source: American Academy of Neurology

Categories : NeurologyTags :

Could a New Way to Restore Lithium Deficiency in Alzheimer’s Really Work?

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Neurons in the brain of an Alzheimer’s patient, with plaques caused by tau proteins. Credit: NIH

It has been known that brain lithium (Li) levels are depleted in individuals with mild cognitive impairment, a precursor for Alzheimer’s disease. For years, there have been attempts to restore Li levels to prevent Alzheimer’s disease by administering lithium carbonate. But now, it has been shown that the Li from this compound has been sequestered and not actually restoring the endogenous Li levels. Now, scientists have tried using lithium oxide (LiO) salts instead – and the treatment appears to be effective in prevention and even reversal of a mouse model of Alzheimer’s.

Join our QuickNews podcast as the arguments for and against this lithium-based approach are unpacked and debated.

Categories : Ageing NeurologyTags :

Poor Sleep May Accelerate Brain Ageing

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Poor sleep may accelerate brain ageing, a new study shows. Photo by Andrea Piacquadio

People who sleep poorly are more likely than others to have brains that appear older than they actually are. This is according to a comprehensive brain imaging study from Karolinska Institutet, published in the journal eBioMedicine. Increased inflammation in the body may partly explain the association.

Poor sleep has been linked to dementia, but it is unclear whether unhealthy sleep habits contribute to the development of dementia or whether they are rather early symptoms of the disease. In a new study, researchers at Karolinska Institutet have investigated the link between sleep characteristics and how old the brain appears in relation to its chronological age. 

The study includes 27 500 middle-aged and older people from the UK Biobank who underwent magnetic resonance imaging (MRI) of the brain. Using machine learning, the researchers estimated the biological age of the brain based on over a thousand brain MRI phenotypes. 

Low-grade inflammation 

The participants’ sleep quality was scored based on five self-reported factors: chronotype (being a morning/evening person), sleep duration, insomnia, snoring, and daytime sleepiness. They were then divided into three groups: healthy (≥ 4 points), intermediate (2-3 points), or poor (≤ 1 point) sleep. 

“The gap between brain age and chronological age widened by about six months for every 1-point decrease in healthy sleep score,” explains Abigail Dove, researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, who led the study. “People with poor sleep had brains that appeared on average one year older than their actual age.” 

To understand how poor sleep can affect the brain, the researchers also examined levels of low-grade inflammation in the body. They found that inflammation could explain just over ten per cent of the link between poor sleep and older brain age. 

“Our findings provide evidence that poor sleep may contribute to accelerated brain ageing and point to inflammation as one of the underlying mechanisms,” says Abigail Dove. “Since sleep is modifiable, it may be possible to prevent accelerated brain ageing and perhaps even cognitive decline through healthier sleep.” 

Several possible explanations 

Other possible mechanisms that could explain the association are negative effects on the brain’s waste clearance system, which is active mainly during sleep, or that poor sleep affects cardiovascular health, which in turn can have a negative impact on the brain. 

Participants in the UK Biobank are healthier than the general UK population, which could limit the generalisability of the findings. Another limitation of the study is that the results are based on self-reported sleep. 

The study was conducted in collaboration with researchers from the Swedish School of Sport and Health Sciences, and Tianjin Medical University and Sichuan University in China, among others. It was funded by the Alzheimer’s Foundation, the Dementia Foundation, the Swedish Research Council, the Loo and Hans Osterman Foundation for Medical Research, and the Knowledge Foundation. The researchers report no conflicts of interest. 

Source: Karolinska Institutet

Categories : NeurologyTags :

No ‘Beneficial’ Level of Alcohol Consumption for Dementia Risk

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Photo by Apolo Photographer on Unsplash

Any amount of alcohol consumption may increase risk of dementia, according to the most comprehensive study of alcohol consumption and dementia risk to date.

Led by the University of Oxford, Yale University, and the University of Cambridge, the research challenges previous suggestions that light-to-moderate drinking may have a protective effect against dementia. The study is published in BMJ Evidence-Based Medicine.

Alcohol consumption is widespread and is linked with an increased risk of many diseases. Heavy drinking has previously been linked to higher risk of dementia. The connection between moderate levels of drinking and higher risk of dementia was uncertain with some studies suggesting that moderate drinking may even reduce dementia risk. However, recent studies involving brain scans have shown that drinking alcohol even at low levels may increase the risk of dementia.

This study combined observational data from more than half a million participants in two large and diverse population studies: the US Million Veteran Program and UK Biobank to assess whether self-reported alcohol use was linked with risk of developing a broad range of types of dementia.

The researchers also investigated links between genetically-predicted likelihood of drinking alcohol and alcohol use disorder for more than 2.4 million participants in 45 individual studies. This approach helped the researchers overcome some of the difficulties in distinguishing correlation from causation.

Key findings:

  • Observational analyses seemed to support previous findings that current low and moderate drinking is associated with lower risk of dementia when compared with non-drinking and heavy drinking; however, some current non-drinkers were previously heavy drinkers, which could account for their increased dementia risk compared to consistently low drinkers;
  • Genetic analyses, however, revealed a continuously increasing trend of higher dementia risk with greater alcohol intakes, suggesting that any level of alcohol consumption increases the risk of dementia, with no evidence that drinking alcohol may have a protective effect;
  • A doubled increase in a person’s genetically-predicted risk of alcohol use disorder was associated with a 16% higher risk of dementia, while a three times higher increase in number of alcoholic drinks per week increased the risk of dementia risk by 15%;
  • The study also showed that people who later developed dementia reduced their alcohol intake before diagnosis, another explanation for prior findings of protective effects of alcohol, rather than true benefit.

Dr Anya Topiwala, Senior Clinical Researcher at Oxford Population Health, Consultant Psychiatrist, and lead author of the study, said ‘Our findings challenge the common belief that low levels of alcohol are beneficial for brain health. Genetic evidence offers no support for a protective effect – in fact, it suggests the opposite. Even light or moderate drinking may increase the risk of dementia, indicating that reducing alcohol consumption across the population could play a significant role in dementia prevention.’

Dr Stephen Burgess, Statistician at the University of Cambridge, said ‘The random nature of genetic inheritance allows us to compare groups with higher and lower levels of alcohol drinking in a way that allows us to make conclusions that untangle the confusion between correlation and causation. Our findings do not only hold for those who have a particular genetic predisposition, but for anyone who chooses to drink, our study suggests that greater alcohol consumption leads to higher risk of dementia.’

Dr Joel Gelernter, Professor at Yale University and senior author of the study, said ‘These results, which add to our understanding of the relationship between alcohol and dementia, have clinical implications – there was a time when medical knowledge seemed to support that light drinking would be beneficial to brain health, and this work adds to the evidence that this is not correct’.

This study adds to growing evidence that alcohol use, even at moderate levels, may have no safe threshold when it comes to brain health, reinforcing the case for preventive strategies that reduce alcohol consumption in the general population.

The study, ‘Alcohol use and risk of dementia in diverse populations: evidence from cohort, case–control and Mendelian randomisation approaches‘, is published in BMJ Evidence-Based Medicine.

Source: Oxford University

Categories : NeurologyTags :

Psychedelics Alter Far More Neurons than Expected

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The discovery challenges decades of assumptions and points to new hope for patients with depression, Alzheimer’s, and beyond

The most basic assumption about how psychedelic medicine works is at least partially flawed: Psychedelics are altering not just a few specific brain cells, but the vast majority of them, according to a new University of Michigan study.

The research, published in Molecular Psychiatry, shows that even neurons without serotonin 2A receptors – which are important for physiological processes, including mood regulation, perception and cognitive functions – can dramatically benefit from psychedelic compounds. This means that the therapeutic use of psychedelic medicine is far broader than currently appreciated, with important implications for Alzheimer’s disease and PTSD.

“We identified brain regions where most neurons are completely lacking serotonin 2A receptors. Surprisingly, psychedelic treatment was still able to strongly boost connectivity onto these neurons,” said the study’s senior author Omar Ahmed, U-M professor of psychology whose lab studies behavioural neural circuits and attempts to repair them when they go awry in specific disorders.

Psychedelic medicine is being successfully used in clinical trials to treat major depression. For decades it has been presumed that psychedelics work therapeutically by targeting the serotonin 2A receptor found on neurons in the frontal cortex and boosting connections onto those neurons. It has been assumed that frontal neurons with this serotonin 2A receptor were the only neurons benefiting from psychedelic therapy. This is why psychedelic medicine has focused on treating conditions relating to frontal dysfunction, such as major depression, Ahmed said.

When the research team studied the genes expressed in neurons of the entire cortex of the brain, they identified brain regions that did not express the serotonin 2A receptor that is supposed to be needed for psychedelic therapy to work. Ahmed’s lab, including co-first authors Tyler Ekins and Chloe Rybicki-Kler, showed that the retrosplenial cortex, a brain region important for memory, orientation and even imagining oneself in the future, was remarkably devoid of these receptors. The retrosplenial cortex is one of the first brain regions to be impaired in Alzheimer’s disease.

The team then recorded from these neurons lacking serotonin 2A receptors and found that they also show robust neuroplasticity (more synapses) after psychedelic treatment.

“This was a very unexpected finding given the current assumptions about how psychedelic medicine works,” Ahmed said.

The next step used a genetic engineering technique called CRISPR-Cas to reveal the rules that govern this surprising boost in brain connectivity, leading to a revised theory of how psychedelics control the brain’s ability to adapt and change. These new rules do not require neurons to have serotonin 2A receptors themselves to receive a synaptic boost from psychedelics, dramatically increasing the number of brain connections that can be potentially repaired by psychedelic medicine.

“The most successful medicines are those where we fully understand how they work. That is why it is so important to understand the fundamentals of how psychedelic medicine actually works,” Ahmed said.

The new findings are cause for both caution and optimism, he said. Caution, because they show that we need to be wary of psychedelics acting on unintended neurons. Optimism, because they open up the possibility of using psychedelic-like compounds to restore brain connections in Alzheimer’s disease and other disorders involving the retrosplenial cortex, such as PTSD.

“We are actively working on essential preclinical research to test this hypothesis related to Alzheimer’s disease,” Ahmed said.

Source: University of Michigan

Categories : Cancer Neurology PaediatricsTags :

Combination of Diet and Medication Reprograms Paediatric Neuroblastoma

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Credit: National Cancer Institute

Researchers at Children’s Hospital of Philadelphia (CHOP) found that combining a specialised diet with an approved medication interrupts the growth of high-risk neuroblastoma, a deadly paediatric cancer, by reprogramming tumour behaviour. The findings were published in the journal Nature.

Neuroblastoma originates from primitive cells meant to form nerve tissues but that remain “undifferentiated,” indicating cancer cells that haven’t specialized, often suggesting a more aggressive and unfavourable prognosis. These tumours rely on a steady supply of chemicals called polyamines that are essential for rapid cell growth and tumour progression. A medicine called difluoromethylornithine (DFMO) was approved by the Food and Drug Administration (FDA) to treat children with high-risk neuroblastoma, as DFMO blocks polyamine production. However, researchers sought to improve the effectiveness of the drug by using it at high doses and combining it with a diet that is depleted of the nutrients used by the body to make polyamines (arginine). This two-step approach was anticipated to lower polyamines substantially more than low dose DFMO alone.

“Our findings show that this treatment reduced polyamines in tumours to roughly 10% of their usual levels. This reduction greatly slowed tumour growth, and in many cases, completely eliminated the tumours,” said Michael D. Hogarty, MD, a lead author and an Attending Physician in the Division of Oncology at Children’s Hospital of Philadelphia. “Notably, the treatment altered the way the tumour cells make proteins, making it harder for them to grow and easier for them to mature, or differentiate.”

Hogarty and his team used a preclinical model to mimic MYCN-driven neuroblastoma, directly addressing the strong association between extra MYCN gene copies and aggressive neuroblastoma with poor prognosis. Animal models with tumours were divided into groups: one fed a normal diet and the other lacking amino acids for polyamine production. Each group either received DFMO in their drinking water or did not. The special diet or DFMO alone partially lowered polyamines and extended survival, but the combination had the most significant impact on tumours due to the profound polyamine depletion it caused.

The researchers plan to conduct additional preclinical studies, followed hopefully by clinical trials in children to determine the safety and efficacy of targeting this specific metabolic dependency of neuroblastoma cells. By complementing existing treatments, they hope to substantially improve patient outcomes, and because the therapy targets polyamines it may be effective in many other types of cancer that have frequent MYC gene activation. 

Source: Children’s Hospital of Philadelphia