Tag: Alzheimer's disease

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How Gamma Rhythm Light and Sound Strips Amyloid in Alzheimer’s Mouse Models

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Studies at MIT and elsewhere are producing mounting evidence that light flickering and sound clicking at the gamma brain rhythm frequency of 40Hz can reduce Alzheimer’s disease (AD) progression and treat symptoms in human volunteers as well as lab mice. In a new study in Nature using a mouse model of the disease, researchers at The Picower Institute for Learning and Memory of MIT reveal a key mechanism that may contribute to these beneficial effects: clearance of amyloid proteins, a hallmark of AD pathology, via the brain’s glymphatic system, a recently discovered “plumbing” network parallel to the brain’s blood vessels.

“Ever since we published our first results in 2016, people have asked me how does it work? Why 40Hz? Why not some other frequency?” said study senior author Li-Huei Tsai, Professor of Neuroscience at Picower. “These are indeed very important questions we have worked very hard in the lab to address.”

The new paper describes a series of experiments, led by Mitch Murdock when he was a Brain and Cognitive Sciences doctoral student at MIT, showing that when sensory gamma stimulation increases 40 Hz power and synchrony in the brains of mice, that prompts a particular type of neuron to release peptides. The study results further suggest that those short protein signals then drive specific processes that promote increased amyloid clearance via the glymphatic system.

“We do not yet have a linear map of the exact sequence of events that occurs,” said Murdock, who was jointly supervised by Tsai and co-author and collaborator Ed Boyden, Professor of Neurotechnology at MIT. “But the findings in our experiments support this clearance pathway through the major glymphatic routes.”

From gamma to glymphatics

Because prior research has shown that the glymphatic system is a key conduit for brain waste clearance and may be regulated by brain rhythms, Tsai and Murdock’s team hypothesised that it might help explain the lab’s prior observations that gamma sensory stimulation reduces amyloid levels in Alzheimer’s model mice.

Working with “5XFAD” mice, which genetically model Alzheimer’s, Murdock and co-authors first replicated the lab’s prior results that 40Hz sensory stimulation increases 40Hz neuronal activity in the brain and reduces amyloid levels. Then they set out to measure whether there was any correlated change in the fluids that flow through the glymphatic system to carry away wastes. Indeed, they measured increases in cerebrospinal fluid in the brain tissue of mice treated with sensory gamma stimulation compared to untreated controls. They also measured an increase in the rate of interstitial fluid leaving the brain. Moreover, in the gamma-treated mice he measured increased diameter of the lymphatic vessels that drain away the fluids and measured increased accumulation of amyloid in cervical lymph nodes, which is the drainage site for that flow.

To investigate how this increased fluid flow might be happening, the team focused on the aquaporin 4 (AQP4) water channel of astrocyte cells, which enables the cells to facilitate glymphatic fluid exchange. When they blocked APQ4 function with a chemical, that prevented sensory gamma stimulation from reducing amyloid levels and prevented it from improving mouse learning and memory. And when, as an added test they used a genetic technique for disrupting AQP4, that also interfered with gamma-driven amyloid clearance.

In addition to the fluid exchange promoted by APQ4 activity in astrocytes, another mechanism by which gamma waves promote glymphatic flow is by increasing the pulsation of neighbouring blood vessels. Several measurements showed stronger arterial pulsatility in mice subjected to sensory gamma stimulation compared to untreated controls.

One of the best new techniques for tracking how a condition, such as sensory gamma stimulation, affects different cell types is to sequence their RNA to track changes in how they express their genes. Using this method, Tsai and Murdock’s team saw that gamma sensory stimulation indeed promoted changes consistent with increased astrocyte AQP4 activity.

Prompted by peptides

The RNA sequencing data also revealed that upon gamma sensory stimulation a subset of neurons, called “interneurons,” experienced a notable uptick in the production of several peptides. This was not surprising in the sense that peptide release is known to be dependent on brain rhythm frequencies, but it was still notable because one peptide in particular, VIP, is associated with Alzheimer’s-fighting benefits and helps to regulate vascular cells, blood flow and glymphatic clearance.

Seizing on this intriguing result, the team ran tests that revealed increased VIP in the brains of gamma-treated mice. The researchers also used a sensor of peptide release and observed that sensory gamma stimulation resulted in an increase in peptide release from VIP-expressing interneurons.

But did this gamma-stimulated peptide release mediate the glymphatic clearance of amyloid? To find out, the team ran another experiment: they chemically shut down the VIP neurons. When they did so, and then exposed mice to sensory gamma stimulation, they found that there was no longer an increase in arterial pulsatility and there was no more gamma-stimulated amyloid clearance.

“We think that many neuropeptides are involved,” Murdock said. Tsai added that a major new direction for the lab’s research will be determining what other peptides or other molecular factors may be driven by sensory gamma stimulation.

Tsai and Murdock added that while this paper focuses on what is likely an important mechanism – glymphatic clearance of amyloid – by which sensory gamma stimulation helps the brain, it’s probably not the only underlying mechanism that matters. The clearance effects shown in this study occurred rather rapidly but in lab experiments and clinical studies weeks or months of chronic sensory gamma stimulation have been needed to have sustained effects on cognition.

With each new study, however, scientists learn more about how sensory stimulation of brain rhythms may help treat neurological disorders.

Source: Picower Institute at MIT

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Yoga Provides Unique Cognitive Benefits to Older Women at Risk of Alzheimer’s disease

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Photo by Mikhail Nilov

A new UCLA Health study found Kundalini yoga provided several benefits to cognition and memory for older women at risk of developing Alzheimer’s disease including restoring neural pathways, preventing brain matter decline and reversing aging and inflammation-associated biomarkers – improvements not seen in a group who received standard memory training exercises.

The findings, published in the journal Translational Psychiatry, are the latest in a series of studies led by UCLA Health researchers over the past 15 years into the comparative effects of yoga and traditional memory enhancement training on slowing cognitive decline and addressing other risk factors of dementia.

Led by UCLA Health psychiatrist Dr. Helen Lavretsky of the Jane and Terry Semel Institute for Neuroscience and Human Behavior, this latest study sought to determine whether Kundalini yoga could be used early on to prevent cognitive decline and trajectories of Alzheimer’s disease among postmenopausal women.

Women have about twice the risk of developing Alzheimer’s disease compared to men due to several factors including longer life expectancy, changes in oestrogen levels during menopause and genetics.

In the new study, a group of more than 60 women ages 50 and older who had self-reported memory issues and cerebrovascular risk factors were recruited from a UCLA cardiology clinic. The women were divided evenly into two groups. The first group participated in weekly Kundalini yoga sessions for 12 weeks while the other one group underwent weekly memory enhancement training during the same time period. Participants were also provided daily homework assignments.

Kundalini yoga is a method that focuses on meditation and breath work more so than physical poses. Memory enhancement training developed by the UCLA Longevity centre includes a variety of exercises, such as using stories to remember items on a list or organising items on a grocery list, to help preserve or improve long-term memory of patients.

Researchers assessed the women’s cognition, subjective memory, depression and anxiety after the first 12 weeks and again 12 weeks later to determine how stable any improvements were. Blood samples were also taken to test for gene expression of aging markers and for molecules associated with inflammation, which are contributing factors to Alzheimer’s disease. A handful of patients were also assessed with MRIs to study changes in brain matter.

Researchers found the Kundalini yoga group participants saw several improvements not experienced by the memory enhancement training group. These included significant improvement in subjective memory complaints, prevention in brain matter declines, increased connectivity in the hippocampus which manages stress-related memories, and improvement in the peripheral cytokines and gene expression of anti-inflammatory and anti-aging molecules.

“That is what yoga is good for – to reduce stress, to improve brain health, subjective memory performance and reduce inflammation and improve neuroplasticity,” Lavretsky said.

Among the memory enhancement training group, the main improvements were found to be in the participants’ long-term memory.

Neither group saw changes in anxiety, depression, stress or resilience, though Lavretsky stated this is likely because the participants were relatively healthy and were not depressed.

While the long-term effects of Kundalini yoga on preventing or delaying Alzheimer’s disease require further study, Lavretsky said the study demonstrates that using yoga and memory training in tandem could provide more comprehensive benefits to the cognition of older women.

“Ideally, people should do both because they do train different parts of the brain and have different overall health effects,” Lavretsky said. “Yoga has this anti-inflammatory, stress-reducing, anti-aging neuroplastic brain effect which would be complementary to memory training.”

Source: University of California – Los Angeles Health Sciences

Categories : Neurodegenerative DiseasesTags :

Difficulty in Navigating could Predict Alzheimer’s Years Before Symptom Onset

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People at risk of Alzheimer’s disease have impaired spatial navigation before they develop problems with other cognitive functions, including memory, finds a new study led by UCL researchers.

The research, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, used virtual reality to test the spatial navigation of 100 asymptomatic midlife adults, aged 43-66, from the PREVENT-Dementia prospective cohort study.

Participants had a hereditary or physiological risk of Alzheimer’s disease, due to either a gene (the APOE-ε4 allele) that puts them at risk of the condition, a family history of Alzheimer’s disease, or lifestyle risk factors such as low levels of physical activity. Crucially, these participants were around 25 years younger than their estimated age of dementia onset.

Led by Professor Dennis Chan, the study used a test designed by Dr Andrea Castegnaro and Professor Neil Burgess (all UCL Institute of Cognitive Neuroscience), in which participants were asked to navigate within a virtual environment while wearing VR headsets.

The researchers found that people at greater risk of developing Alzheimer’s disease, regardless of risk factor, were selectively impaired on the VR navigation task, without a corresponding impairment on other cognitive tests. The authors say their findings suggest that impairments in spatial navigation may begin to develop years, or even decades, before the onset of any other symptoms.

First author, Dr Coco Newton (UCL Institute of Cognitive Neuroscience), who carried out the work while at University of Cambridge said: “Our results indicated that this type of navigation behaviour change might represent the very earliest diagnostic signal in the Alzheimer’s disease continuum — when people move from being unimpaired to showing manifestation of the disease.”

The researchers also found that there was a strong gender difference in how participants performed, with the impairment being observed in men and not women.

Dr Newton added: “We are now taking these findings forward to develop a diagnostic clinical decision support tool for the NHS in the coming years, which is a completely new way of approaching diagnostics and will hopefully help people to get a more timely and accurate diagnosis.

“This is particularly important with the emergence of anti-amyloid treatments for Alzheimer’s, which are considered to be most effective in the earliest stages of the disease.

“It also highlights the need for further study of the differing vulnerability of men and women to Alzheimer’s disease and the importance of taking gender into account for both diagnosis and future treatment.”

Professor Chan said: “We are excited by these findings for two main reasons. First, they improve detection of the clinical onset of Alzheimer’s disease, critical for prompt application of treatments.

“Second, the VR navigation test is based on our knowledge of the spatial properties of cells in the brain’s temporal lobe, and the application of cellular neuroscience to clinical populations helps bridge the gap in understanding how disease at the neuronal level can result in the clinical manifestation of disease. This knowledge gap currently represents one of the biggest barriers to progress in Alzheimer’s research.”

Source: University College London

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Alzheimer’s Disease Cases Caused by Growth Hormone Treatment

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

Five cases of Alzheimer’s are believed to have arisen as a result of medical treatments decades earlier, according to a new paper published in Nature Medicine. Alzheimer’s disease is caused by the amyloid-beta protein, and is usually a sporadic condition of late adult life, or more rarely as an inherited condition from a faulty gene.

The study, by a team of UCL and UCLH researchers, provides the first evidence of Alzheimer’s disease in living people that appears to have been medically acquired and due to transmission of the amyloid-beta protein.

The people described in the paper had all been treated as children with a type of human growth hormone extracted from pituitary glands from deceased individuals (cadaver-derived human growth hormone or c-hGH). This was used to treat at least 1848 people in the UK between 1959 and 1985, and used for various causes of short stature.

It was withdrawn in 1985 after it was recognised that some c-hGH batches were contaminated with prions (infectious proteins) which had caused Creutzfeldt-Jakob disease (CJD) in some people.

c-hGH was then replaced with synthetic growth hormone that did not carry the risk of transmitting CJD.

These researchers previously reported that some patients with CJD due to c-hGH treatment (called iatrogenic CJD) also had prematurely developed deposits of the amyloid-beta protein in their brains.* The scientists went on to show in a 2018 paper that archived samples of c-hGH were contaminated with amyloid-beta protein and, despite having been stored for decades, transmitted amyloid-beta pathology to laboratory mice when it was injected.

They suggested that individuals exposed to contaminated c-hGH, who did not succumb to CJD and lived longer, might eventually develop Alzheimer’s disease.

This latest paper reports on eight people referred to UCLH’s National Prion Clinic at the National Hospital for Neurology and Neurosurgery in London, who had all been treated with c-hGH in childhood, often over several years.

Five of these people had symptoms of dementia, and either had already been diagnosed with Alzheimer’s disease or would otherwise meet the diagnostic criteria for this condition; another person met criteria for mild cognitive impairment. These people were between 38 and 55 years old when neurological symptoms started. Biomarker analyses supported the diagnoses of Alzheimer’s disease in two patients with the diagnosis, and was suggestive of Alzheimer’s in one other person; an autopsy analysis showed Alzheimer’s pathology in another patient.

The unusually young age at which these patients developed symptoms suggests they did not have the usual sporadic Alzheimer’s which is associated with old age. In the five patients in whom samples were available for genetic testing, the team ruled out inherited Alzheimer’s disease.

As c-hGH treatment is no longer used, there is no risk of any new transmission via this route. There have been no reported cases of Alzheimer’s acquired from any other medical or surgical procedures. There is no suggestion that amyloid-beta can be passed on in day-to-day life or during routine medical or social care.

However, the researchers caution that their findings highlight the importance of reviewing measures to ensure there is no risk of accidental transmission of amyloid-beta via other medical or surgical procedures which have been implicated in accidental transmission of CJD.

The lead author of the research, Professor John Collinge, Director of the UCL Institute of Prion Diseases and a consultant neurologist at UCLH, said: “There is no suggestion whatsoever that Alzheimer’s disease can be transmitted between individuals during activities of daily life or routine medical care. The patients we have described were given a specific and long-discontinued medical treatment which involved injecting patients with material now known to have been contaminated with disease-related proteins.

“However, the recognition of transmission of amyloid-beta pathology in these rare situations should lead us to review measures to prevent accidental transmission via other medical or surgical procedures, in order to prevent such cases occurring in future.

“Importantly, our findings also suggest that Alzheimer’s and some other neurological conditions share similar disease processes to CJD, and this may have important implications for understanding and treating Alzheimer’s disease in the future.”

Source: University College London

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Crafting a ‘Key’ to Cross the Blood-brain Boundary

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Researchers led by Michael Mitchell of the University of Pennsylvania are close to gaining access through the blood-brain barrier, a long-standing boundary in biology, by granting molecules a special ‘key’ to gain access.

Their findings, published in the journal Nano Letters, present a model that uses lipid nanoparticles (LNPs) to deliver mRNA, offering new hope for treating conditions like Alzheimer’s disease and seizures.

“Our model performed better at crossing the blood-brain barrier than others and helped us identify organ-specific particles that we later validated in future models,” says Mitchell, associate professor of bioengineering at Penn’s School of Engineering and Applied Science, and senior author on the study.

“It’s an exciting proof of concept that will no doubt inform novel approaches to treating conditions like traumatic brain injury, stroke, and Alzheimer’s.”

Search for the key

To develop the model, Emily Han, a PhD candidate and NSF Graduate Research Fellow in the Mitchell Lab and first author of the paper, explains that it started with a search for the right in vitro screening platform, saying, “I was combing through the literature, most of the platforms I found were limited to a regular 96-well plate, a two-dimensional array that can’t represent both the upper and lower parts of the blood-brain barrier, which correspond to the blood and brain, respectively.”

Han then explored high-throughput transwell systems with both compartments but found they didn’t account for mRNA transfection of the cells, revealing a gap in the development process.

This led her to create a platform capable of measuring mRNA transport from the blood compartment to the brain, as well as transfection of various brain cell types including endothelial cells and neurons.

“I spent months figuring out the optimal conditions for this new in vitro system, including which cell growth conditions and fluorescent reporters to use,” Han explains.

“Once robust, we screened our library of LNPs and tested them on animal models. Seeing the brains express protein as a result of the mRNA we delivered was thrilling and confirmed we were on the right track.”

The team’s platform is poised to significantly advance treatments for neurological disorders.

It’s currently tailored for testing a range of LNPs with brain-targeted peptides, antibodies, and various lipid compositions.

However, it could also deliver other therapeutic agents like siRNA, DNA, proteins, or small molecule drugs directly to the brain after intravenous administration.

What’s more, this approach isn’t limited to the blood-brain barrier as it shows promise for exploring treatments for pregnancy-related diseases by targeting the blood-placental barrier, and for retinal diseases focusing on the blood-retinal barrier.

Next Steps

The team is eager to use this platform to screen new designs and test their effectiveness in different animal models.

They are particularly interested in working with collaborators with advanced animal models of neurological disorders.

“We’re collaborating with researchers at Penn to establish brain disease models,” Han says.

“We’re examining how these LNPs impact mice with various brain conditions, ranging from glioblastoma to traumatic brain injuries. We hope to make inroads towards repairing the blood-brain barrier or target neurons damaged post-injury.”

Source: University of Pennsylvania

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Could Bizarre Visual Symptoms Be a Telltale Sign of Alzheimer’s?

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Photo by Mari Lezhava on Unsplash

A team of international researchers, led by UC San Francisco, has completed the first large-scale study of posterior cortical atrophy, a baffling constellation of visuospatial symptoms that present as the first signs of Alzheimer’s disease. These symptoms occur in up to 10% of cases of Alzheimer’s disease.

The study, which appears in The Lancet Neurology,  includes data from more than 1000 patients at 36 sites in 16 countries.

Posterior cortical atrophy (PCA) overwhelmingly predicts Alzheimer’s, the researchers found. Some 94% of the PCA patients had Alzheimer’s pathology and the remaining 6% had conditions like Lewy body disease and frontotemporal lobar degeneration. In contrast, other studies show that 70% of patients with memory loss have Alzheimer’s pathology.

Unlike memory issues, patients with PCA struggle with judging distances, distinguishing between moving and stationary objects and completing tasks like writing and retrieving a dropped item despite a normal eye exam, said co-first author Marianne Chapleau, PhD, of the UCSF Department of Neurology, the Memory and Aging Center and the Weill Institute for Neurosciences.

Most patients with PCA have normal cognition early on, but by the time of their first diagnostic visit, an average 3.8 years after symptom onset, mild or moderate dementia was apparent with deficits identified in memory, executive function, behaviour, and speech and language, according to the researchers’ findings.

At the time of diagnosis, 61% demonstrated “constructional dyspraxia,” an inability to copy or construct basic diagrams or figures; 49% had a “space perception deficit,” difficulties identifying the location of something they saw; and 48% had “simultanagnosia,” an inability to visually perceive more than one object at a time. Additionally, 47% faced new challenges with basic math calculations and 43% with reading.

We need better tools and training to identify patients

“We need more awareness of PCA so that it can be flagged by clinicians,” said Chapleau. “Most patients see their optometrist when they start experiencing visual symptoms and may be referred to an ophthalmologist who may also fail to recognise PCA,” she said. “We need better tools in clinical settings to identify these patients early on and get them treatment.”

The average age of symptom onset of PCA is 59, several years younger than the typical memory symptoms of Alzheimer’s. This is another reason why patients with PCA are less likely to be diagnosed, Chapleau added.

Early identification of PCA may have important implications for Alzheimer’s treatment, said co-first author Renaud La Joie, PhD, also of the UCSF Department of Neurology and the Memory and Aging Center. In the study, levels of amyloid and tau, identified in cerebrospinal fluid and imaging, as well as autopsy data, matched those found in typical Alzheimer’s cases. As a result, patients with PCA may be candidates for anti-amyloid therapies, like lecanemab (Leqembi), approved by the U.S Food and Drug Administration in January 2023, and anti-tau therapies, currently in clinical trials, both of which are believed to be more effective in the earliest phases of the disease, he said.

“Patients with PCA have more tau pathology in the posterior parts of the brain, involved in the processing of visuospatial information, compared to those with other presentations of Alzheimer’s. This might make them better suited to anti-tau therapies,” he said.

Patients have mostly been excluded from trials, since they are “usually aimed at patients with amnestic Alzheimer’s with low scores on memory tests,” La Joie added. “However, at UCSF we are considering treatments for patients with PCA and other non-amnestic variants.”

Better understanding of PCA is “crucial for advancing both patient care and for understanding the processes that drive Alzheimer’s disease,” said senior author Gil Rabinovici, MD, director of the UCSF Alzheimer’s Disease Research Center. “It’s critical that doctors learn to recognise the syndrome so patients can receive the correct diagnosis, counseling and care.

“From a scientific point of view, we really need to understand why Alzheimer’s is specifically targeting visual rather than memory areas of the brain. Our study found that 60% of patients with PCA were women – better understanding of why they appear to be more susceptible is one important area of future research.”

Source: University of California San Francisco

Categories : Mental HealthTags :

Visions of Nonphysical World are Common Among Cognitively Healthy American Indians

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Visual hallucinations are common among people with Lewy body dementia and other types of dementia. Identifying visual hallucinations is an important component of a wide variety of medical and psychiatric diagnoses and treatments, but without cultural context, some patients’ symptoms can be misinterpreted or misdiagnosed.

There is little in medical literature about normal spiritual experiences in American Indian participants in the context of a neurocognitive evaluation. University of Minnesota Medical School researchers sought to understand how the culture and spirituality of the American Indian Ojibwe tribe affect a doctor’s assessment of normal aging.

Publishing in JAMA Network Open, the research team found that visions of the nonphysical world are common among cognitively healthy Ojibwe individuals and can represent normal spiritual experiences. 

“Consideration of a patient’s cultural background and belief system can help avert erroneous disqualification for disease-modifying therapy, exclusion from clinical trials and all the negative ramifications associated with a misdiagnosis of psychiatric disease,” said William Mantyh, MD, an assistant professor at the University of Minnesota Medical School and  behavioural neurologist with M Health Fairview.

In partnership with an Ojibwe Tribal Nation in Minnesota, the study recruited 33 cognitively healthy tribal elders aged 55 years or older. The research found 48% of participants reported frequent transient visions of the nonphysical world that generally were benevolent and involved spiritual beings and/or ancestors. 

According to the research team, clinicians would benefit from careful consideration of cultural or spiritual context to avoid misdiagnosis of neuropsychiatric disease. 

“Today’s environment of infrequent or insufficiently short cognitive evaluations – an average 16-minute face-to-face visit with a physician and increasing use of pre-visit symptom checklists increase the risk of falsely attributing a spiritual experience to a hallucination,” said Dr Mantyh. 

Dr Mantyh and his research team’s overarching goal is to ensure accurate diagnosis of neurodegenerative disease in American Indian communities. To reach this goal, the research team is including American Indian participants in the development of a new Alzheimer’s disease blood test. So far, more than 250 participants have been included. These new Alzheimer’s disease blood tests, up to 95% accurate, directly detect the proteins related to Alzheimer’s disease in the blood, but they also look at a patient’s APOE ε4 gene. APOE ε4 is the most significant genetic risk factor for Alzheimer’s disease, but its effect on Alzheimer’s disease depends on a patient’s ancestry. 

Source: University of Minnesota

Categories : Neurodegenerative Diseases NeurologyTags :

Could Stimulating Gamma Brain Waves Help Treat Alzheimer’s?

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A review in the Journal of Internal Medicine explores the potential of non-invasive interventions such as light, sound, and magnets to stimulate gamma brain waves for the treatment of Alzheimer’s disease. Such strategies may be beneficial because Alzheimer’s disease is characterised by reduced fast brain oscillations in the gamma range (30–100Hz).

The authors note that recent studies reveal that it is feasible and safe to induce 40Hz brain activity in patients with Alzheimer’s disease through a range of methods. Also, preliminary evidence suggests that such treatment can yield beneficial effects on brain function, disease pathology, and cognitive function in patients.

Various cells in the brain beyond neurons, including microglial cells, astrocytes and vascular cells, seem to be involved in mediating these effects.

“We found that increased gamma activity elicited by the non-invasive 40Hz sensory stimulation profoundly alters the cellular state of various glial cell types,” said corresponding author Li-Huei Tsai, PhD, of MIT. “We are actively investigating the mechanism by which the 40Hz brain activity recruits diverse cell types in the brain to provide neuroprotective effects.”

Source: Wiley

Categories : Neurodegenerative DiseasesTags :

Light Therapy may Improve Symptoms of Alzheimer’s Disease

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New meta-analysis included 15 randomised controlled trials involving 598 patients with Alzheimer’s disease and found improvements in sleep and psycho-behavioural symptoms.

Photo by Matteo Vistocco on Unsplash

Light therapy leads to significant improvements in sleep and psycho-behavioural symptoms for patients with Alzheimer’s disease, according to a new study published this week in the open-access journal PLOS ONE by Qinghui Meng of Weifang Medical University, China, and colleagues.

The cognitive decline associated with Alzheimer’s disease is often accompanied by sleep disturbances and psycho-behavioural symptoms including apathetic and depressive behaviour, agitation and aggression. Photobiomodulation is a non-pharmacological therapy that uses light energy to stimulate the suprachiasmic nucleus (SCN), a sleep modulator in the brain. Despite light therapy receiving increased attention as a potential intervention for Alzheimer’s, a systematic evaluation of its efficacy and safety has been unavailable.

In the new study, researchers searched multiple research databases to identify all randomised controlled trials related to light therapy intervention for Alzheimer’s disease or dementia. Fifteen high-quality trials with available methods and relevant outcomes were selected for further analysis. The included trials were written in English, published between 2005 and 2022, and performed in seven countries. They included a combined 598 patients.

The meta-analysis of all fifteen trials found that light therapy significantly improved sleep efficiency, increased interdaily stability (a measure of the strength of circadian rhythms), and reduced intradaily variability (a measure of how frequently someone transitions between rest and activity during the day). In patients with Alzheimer’s disease, light therapy also alleviated depression and reduced patient agitation and caregiver burden.

Given the limited sample sizes in studies included in this meta-analysis, the authors advocate for larger future studies, which could also explore if bright light exposure could cause any adverse behaviour in patients. They conclude that light therapy is a promising treatment option for some symptoms of Alzheimer’s disease.  

The authors add: “Light therapy improves sleep and psycho-behavioral symptoms in patients with Alzheimer’s disease and has relatively few side effects, suggesting that it may be a promising treatment option for patients with Alzheimer’s disease.”

Provided by PLOS One

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

Nanoparticles from Coffee Grounds could Stall Neurodegenerative Disease Development

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Photo by Mike Kenneally on Unsplash

Researchers may potentially have found a preventive solution for neurodegenerative disorders in the most unlikely of sources: used coffee grounds. The researchers found caffeic-acid based Carbon Quantum Dots (CACQDs) have the potential to protect brain cells from the damage caused by several neurodegenerative diseases – if the condition is triggered by factors such as obesity, age and exposure to pesticides and other toxic environmental chemicals.

Carbon Quantum Dots are essentially simple nanoparticles made of carbon that have found a growing number of applications, including bioimaging thanks to its fluorescent properties and as photochemical catalysts. Their active surfaces can be doped with different elements for desired effects, are biocompatible and can be produced simply from a range of organic substances such as lemon juice and used tea leaves.

The University of Texas at El Paso team behind the study was led by Jyotish Kumar, a doctoral student in the Department of Chemistry and Biochemistry, and overseen by Mahesh Narayan, PhD, a professor and Fellow of the Royal Society of Chemistry in the same department. Their work is described in the journal Environmental Research.

“Caffeic-acid based Carbon Quantum Dots have the potential to be transformative in the treatment of neurodegenerative disorders,” Kumar said.

“This is because none of the current treatments resolve the diseases; they only help manage the symptoms. Our aim is to find a cure by addressing the atomic and molecular underpinnings that drive these conditions.”

Neurodegenerative diseases, when they are in their early stages and are caused by lifestyle or environmental factors, share several traits.

These include elevated levels of free radicals in the brain, and the aggregation of fragments of amyloid-forming proteins that can lead to plaques or fibrils in the brain.

Kumar and his colleagues found that CACQDs were neuroprotective across test tube experiments, cell lines and other models of Parkinson’s disease when the disorder was caused by a pesticide called paraquat.

The CACQDs, the team observed, were able to remove free radicals or prevent them from causing damage and inhibited the aggregation of amyloid protein fragments without causing any significant side effects.

The team hypothesises that in humans, in the very early stage of a condition such as Alzheimer’s or Parkinson’s, a treatment based on CACQDs can be effective in preventing full-on disease.

“It is critical to address these disorders before they reach the clinical stage,” Narayan said.

“At that point, it is likely too late. Any current treatments that can address advanced symptoms of neurodegenerative disease are simply beyond the means of most people. Our aim is to come up with a solution that can prevent most cases of these conditions at a cost that is manageable for as many patients as possible.”

Caffeic acid belongs to a family of compounds called polyphenols, which are plant-based compounds known for their antioxidant, or free radical-scavenging properties. Caffeic acid is unique because it can penetrate the blood-brain barrier and is thus able to exert its effects upon the cells inside the brain, Narayan said.

In the simple one-step ‘green chemistry’ method, the team ‘cooked’ caffeic acid at 230°C for two hours to reorient the caffeic acid’s carbon structure and form CACQDs. The CACQDs were then extracted according to a molecular weight cutoff of 1kDa.

The sheer abundance of coffee grounds is what makes the process both economical and sustainable, Narayan said.

Source: University of Texas at El Paso