Tag: Alzheimer's disease

Categories : Neurodegenerative DiseasesTags :

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

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Source: Pixabay CC0

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

Categories : Ageing Neurodegenerative DiseasesTags :

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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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

Categories : Neurodegenerative DiseasesTags :

Surgery-free Deep Brain Stimulation Could be New Treatment for Dementia

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A new form of deep brain stimulation offers hope for an alternative treatment option for dementia, without the need for surgery.

Researchers at Imperial College London are leading the development of the technique, known as temporal interference (TI). This non-invasive method works by delivering electrical fields to the brain through electrodes placed on the patient’s scalp and head. Their initial findings, which are published in the journal Nature Neuroscience, could lead to an alternative treatment for brain diseases such as Alzheimer’s, and its associated memory loss.

Temporal interference

By targeting the overlapping electrical fields researchers were able to stimulate an area deep in the brain called the hippocampus, without affecting the surrounding areas – a procedure that until now required surgery to implant electrodes into the brain.

The approach has been successfully trialled with 20 healthy volunteers for the first time by a team at the UK Dementia Research Institute (UK DRI) at Imperial and the University of Surrey.

Their initial results show that when healthy adults perform a memory task whilst receiving TI stimulation it helped to improve memory function.

The team is now conducting a clinical trial in people with early-stage Alzheimer’s disease, where they hope TI could be used to improve symptoms of memory loss.

Dr Nir Grossman, from the Department of Brain Sciences at Imperial College London, who led the work said: “Until now, if we wanted to electrically stimulate structures deep inside the brain, we needed to surgically implant electrodes which of course carries risk for the patient, and can lead to complications.

“With our new technique we have shown for the first time, that it is possible to remotely stimulate specific regions deep within the human brain without the need for surgery. This opens up an entirely new avenue of treatment for brain diseases like Alzheimer’s which affect deep brain structures.”

Reaching deep brain regions

TI was first described by the team at Imperial College London in 2017 and shown to work in principle in mice.

This latest work, funded and carried out through the UK Dementia Research Institute, shows for the first time that TI is effective at stimulating regions deep within the human brain.

According to the researchers, this could have broad applications and will enable scientists to stimulate different deep brain regions to discover more about their functional roles, accelerating the discovery of new therapeutic targets.

Source: Imperial College London

Categories : Neurodegenerative DiseasesTags :

Difficulty with Turning when Walking could be a Sign of Early Alzheimer’s

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In a study published in Current Biology, people with early Alzheimer’s disease were found to have difficulty turning when walking. The new study used virtual reality and a computational model to further explore the intricacies of navigational errors previously observed in Alzheimer’s disease.

Researchers, led by Professor Neil Burgess and colleagues in the Space and Memory group at the UCL Institute of Cognitive Neuroscience, grouped participants into three categories: healthy younger participants (31 total), healthy elderly participants (36 total) and patients with mild cognitive impairment (43 total). They then asked them to complete a task while wearing virtual reality goggles, which allowed them to make real movements.

In the trial, participants walked an outbound route guided by numbered cones, consisting of two straight legs connected by a turn. They then had to return to their starting position unguided.

The task was performed under three different environmental conditions aimed at stressing the participant’s navigational skills: an unchanged virtual environment, the ground details being replaced by a plain texture, and the temporary removal of all landmarks from the virtual reality world.

The researchers found that people with early Alzheimer’s consistently overestimated the turns on the route and showed increased variability in their sense of direction. However, these specific impairments were not observed in the healthy older participants or people with mild cognitive impairment, who did not show underlying signs of Alzheimer’s.

This suggests that these navigational errors are specific to Alzheimer’s disease – rather than an extension of healthy ageing or general cognitive decline – and could help with diagnosis.

Joint first author, Dr Andrea Castegnaro (UCL Institute of Cognitive Neuroscience), said: “Our findings offer a new avenue for the early diagnosis of Alzheimer’s disease by focusing on specific navigational errors. However, we know that more work is needed to confirm these early findings.

Dr Castegnaro added, “Cognitive assessments are still needed to understand when the first cognitive impairments develop, and when it comes to existing spatial memory tests used in clinics, those often rely on verbal competence. Our tests aim to offer a more practical tool that doesn’t rely on language or cultural background.”

Source: University College of London

Categories : Cardiovascular Disease Neurodegenerative DiseasesTags :

Keeping Cardiovascular Risk in Check Safeguards against Dementia

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Credit: Centro Nacional de Investigaciones Cardiovasculares

A study published in The Lancet Healthy Longevity shows that brain metabolism, detected with advanced imaging techniques, declines more sharply in middle-aged people with a sustained high cardiovascular risk over 5 years

Cardiovascular disease and dementia frequently occur together in elderly people. Nevertheless, few longitudinal studies have examined how atherosclerosis and its associated risk factors affect brain health from middle age. Now, a new study by scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid provides new data on this relationship; the results confirm the importance of controlling traditional cardiovascular risk factors, such as hypertension, cholesterol, diabetes, smoking, and a sedentary lifestyle, not only to preserve cardiovascular health, but also to prevent Alzheimer’s disease and other dementias. 

The CNIC study shows that atherosclerosis (accumulation of fatty deposits in the arteries) and its associated risk factors, in addition to being the main cause of cardiovascular disease, are also implicated in the cerebral alterations typically found in Alzheimer’s disease, the most frequent cause of dementia.

According to study author Dr Valentín Fuster, CNIC General Director, the new findings are important because they open up the possibility of treating a modifiable disorder, ie cardiovascular disease, to prevent the development a presently untreatable disease – dementia. “The sooner we act to control cardiovascular risk factors, the better it is for our brain health,” said Dr. Fuster.

“Everybody knows that a healthy lifestyle and controlling cardiovascular risk factors are important for preventing a heart attack,” continued Dr Fuster. “Nevertheless, the additional information linking the same risk factors to a decline in brain health could further increase awareness of the need to acquire healthy habits from the earliest life stages.”

In 2021, CNIC scientists discovered that the presence of cardiovascular risk factors and subclinical (presymptomatic) atherosclerosis in the carotid arteries (the arteries that supply the brain) was associated with lower glucose metabolism in the brains of apparently healthy 50-year-old participants in the PESA-CNIC-Santander study. Glucose metabolism in the brain is considered an indicator of brain health.

The PESA-CNIC-Santander study directed by Dr Fuster is a prospective study that includes more than 4000 asymptomatic middle-aged participants who have been exhaustively assessed for the presence and progression of subclinical atherosclerosis since 2010.

Dr Fuster’s team, led by Drs Marta Cortés Canteli and Juan Domingo Gispert, have continued to monitor the cerebral health of these participants over 5 years. Their research shows that individuals who maintained a high cardiovascular risk throughout this period had a more pronounced reduction in cerebral glucose metabolism, detected using imaging techniques such as positron emission tomography (PET).

“In participants with a sustained high cardiovascular risk, the decline in cerebral metabolism was three times greater than in participants who maintained a low cardiovascular risk,” commented Catarina Tristão-Pereira, first author on the study and INPhINIT fellow.

Glucose is the main energy source for neurons and other brain cells. “If there is a sustained decline in cerebral glucose consumption over several years, this may limit the brain ability to withstand neurodegenerative or cerebrovascular diseases in the future,” explained Dr Gispert, an expert in neuroimaging at the CNIC and Barcelonaβeta Research Center.

Through a collaboration with Drs Henrik Zetterberg and Kaj Blennow, world experts in the identification of new blood biomarkers at the University of Gothenburg in Sweden, the CNIC team discovered that the individuals showing this metabolic decline already show signs of neuronal injury. “This is a particularly important finding because neuronal death is irreversible”, said Dr. Cortés Canteli, a neuroscientist at the CNIC and a Miguel Servet fellow at the Fundación Jiménez Díaz Health Research Institute.

The CNIC team also discovered that the progression of subclinical atherosclerosis in the carotid arteries over five years is linked to a metabolic decline in brain regions vulnerable to Alzheimer’s disease, in addition to the effect of cardiovascular risk factors. “These results provide yet another demonstration that the detection of subclinical atherosclerosis with imaging techniques provides highly relevant information,” said Dr Fuster, who is the principal investigator on the PESA study. “The interaction between the brain and the heart is a fascinating topic, and with this study we have seen that this relationship begins much earlier than was thought.”

The scientists conclude that, “carotid screening has great potential to identify individuals at risk of cerebral alterations and cognitive decline in the future.” In the published article they write, “this work could have important implications for clinical practice since it supports the implementation of primary cardiovascular prevention strategies early in life as a valuable approach for a  healthy cerebral longevity.”

“Although we still don’t know what impact this decline in cerebral metabolism has on cognitive function, the detection of neuronal injury in these individuals shows that the earlier we start to control cardiovascular risk factors, the better it will be for our brain,” concluded Dr Cortés Canteli.

Source: CNIC

Categories : Neurodegenerative DiseasesTags :

Study Shows that Intermittent Fasting Might Improve Alzheimer’s Symptoms

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Circadian disruption is a hallmark of Alzheimer’s disease, affecting nearly 80% of patients with issues such as difficulty sleeping and worsening cognitive function at night. Currently there are no treatments for Alzheimer’s that target this aspect of the disease.

A new study in Cell Metabolism from researchers at University of California San Diego School of Medicine has shown in mice that it is possible to correct the circadian disruptions seen in Alzheimer’s disease with time-restricted feeding, a type of intermittent fasting focused on limiting the daily eating window without limiting the amount of food consumed.

In the study, mice that were fed on a time-restricted schedule showed improvements in memory and reduced accumulation of amyloid proteins in the brain. The authors say the findings will likely result in a human clinical trial.

“For many years, we assumed that the circadian disruptions seen in people with Alzheimer’s are a result of neurodegeneration, but we’re now learning it may be the other way around – circadian disruption may be one of the main drivers of Alzheimer’s pathology,” said senior study author Paula Desplats, PhD, professor at UC San Diego School of Medicine. “This makes circadian disruptions a promising target for new Alzheimer’s treatments, and our findings provide the proof-of-concept for an easy and accessible way to correct these disruptions.”

People with Alzheimer’s experience a variety of disruptions to their circadian rhythms, including changes to their sleep/wake cycle, increased cognitive impairment and confusion in the evenings, and difficulty falling and staying asleep.

“Circadian disruptions in Alzheimer’s are the leading cause of nursing home placement,” said Desplats. “Anything we can do to help patients restore their circadian rhythm will make a huge difference in how we manage Alzheimer’s in the clinic and how caregivers help patients manage the disease at home.”

Boosting the circadian clock is an emerging approach to improving health outcomes, and one way to accomplish this is by controlling the daily cycle of feeding and fasting. The researchers tested this strategy in a mouse model of Alzheimer’s disease, feeding the mice on a time-restricted schedule where they were only allowed to eat within a six-hour window each day. For humans, this would translate to about 14 hours of fasting each day.

Compared to control mice who were provided food at all hours, mice fed on the time-restricted schedule had better memory, were less hyperactive at night, followed a more regular sleep schedule and experienced fewer disruptions during sleep. The test mice also performed better on cognitive assessments than control mice, demonstrating that the time-restricted feeding schedule was able to help mitigate the behavioral symptoms of Alzheimer’s disease.

The researchers also observed improvements in the mice on a molecular level. In mice fed on a restricted schedule, the researchers found that multiple genes associated with Alzheimer’s and neuroinflammation were expressed differently. They also found that the feeding schedule helped reduce the amount of amyloid protein that accumulated in the brain. Amyloid deposits are one of the most well-known features of Alzheimer’s disease.

Because the time-restricted feeding schedule was able to substantially change the course of Alzheimer’s in the mice, the researchers are optimistic that the findings could be easily translatable to the clinic, especially since the new treatment approach relies on a lifestyle change rather than a drug.

“Time-restricted feeding is a strategy that people can easily and immediately integrate into their lives,” said Desplats. “If we can reproduce our results in humans, this approach could be a simple way to dramatically improve the lives of people living with Alzheimer’s and those who care for them.”