Category: Neurodegenerative Diseases

Light Therapy may Improve Symptoms of Alzheimer’s Disease

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

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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

Abnormally High Levels of HDL-C Linked to Dementia in Older Adults

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Abnormally high levels of high density lipoprotein cholesterol (HDL-C), are associated with an increased risk of dementia in older adults, according to study led by Monash University. Researchers said very high levels of the ‘good cholesterol’ HDL-C linked to dementia risk in this study were uncommon and not diet related, but more likely to reflect a metabolic disorder. The findings may help doctors to recognise a group of older patients potentially at risk of dementia, particularly in those aged 75 and older.

Published in The Lancet Regional Health – Western Pacific, this is one of the largest studies of elevated HDL-C levels and dementia in initially healthy older people aged mostly over 70, enrolled in the ASPREE* study.

Over an average 6.3 years, participants with very high HDL-C (> 80mg/dL or > 2.07mmol/L) at study entry were observed to have a 27% higher risk of dementia compared to participants with optimal HDL-C levels, while those aged 75 years and older also showed a 42% increased risk compared to those with optimal levels.

Very high HDL-C levels were categorised as 80mg/dL (> 2.07mmol/L) or above.

The optimal level of HDL-C of 40 to 60mg/dL (1.03–1.55mmol/L) for men and 50 to 60mg/dL (1.55–2.07mmol/L) for women was generally beneficial for heart health.

Among 18 668 participants included in this analysis, 2709 had very high HDL-C at study entry, with 38 incidents of dementia in those aged less than 75 years with very high levels, and 101 in those aged 75 and more with very high levels.

First author and Monash University School of Public Health and Preventive Medicine senior research fellow Dr Monira Hussain said that further research was needed to explain why a very high HDL cholesterol level appeared to affect the risk of dementia.

Dr Hussain said these study findings could help improve our understanding of the mechanisms behind dementia, but more research was required.

“While we know HDL cholesterol is important for cardiovascular health, this study suggests that we need further research to understand the role of very high HDL cholesterol in the context of brain health,” she said.

“It may be beneficial to consider very high HDL cholesterol levels in prediction algorithms for dementia risk.”

*The Aspirin in Reducing Events in the Elderly (ASPREE) trial is a double-blind, randomised, placebo-controlled trial of daily aspirin in healthy older people. 

Source: Monash University

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

Nanoplastics Promote Conditions for the Development of Parkinson’s

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Tiny fragments of plastic known as nanoplastics interact with a particular protein that is naturally found in the brain, creating changes linked to Parkinson’s disease and some types of dementia, according to a Duke University-led study.

In Science Advances, the researchers report that the findings create a foundation for a new area of investigation, fuelled by the timely impact of environmental factors on human biology.

“Parkinson’s disease has been called the fastest growing neurological disorder in the world,” said principal investigator, Andrew West, PhD, professor at Duke University School of Medicine.

“Numerous lines of data suggest environmental factors might play a prominent role in Parkinson’s disease, but such factors have for the most part not been identified.”

Improperly disposed plastics have been shown to break into very small pieces and accumulate in water and food supplies, and were found in the blood of most adults in a recent study.

“Our study suggests that the emergence of micro and nanoplastics in the environment might represent a new toxin challenge with respect to Parkinson’s disease risk and progression,” West said.

“This is especially concerning given the predicted increase in concentrations of these contaminants in our water and food supplies.”

West and colleagues in Duke’s Nicholas School of the Environment and the Department of Chemistry at Trinity College of Arts and Sciences found that nanoparticles of the plastic polystyrene — typically found in single use items such as disposable drinking cups and cutlery — attract the accumulation of the protein known as alpha-synuclein.

West said the study’s most surprising findings are the tight bonds formed between the plastic and the protein within the area of the neuron where these accumulations are congregating, the lysosome.

Researchers said the plastic-protein accumulations happened across three different models performed in the study – in test tubes, cultured neurons, and mouse models of Parkinson’s disease.

West said that questions remain about how such interactions might be happening within humans and whether the type of plastic might play a role.

“While microplastic and nanoplastic contaminants are being closely evaluated for their potential impact in cancer and autoimmune diseases, the striking nature of the interactions we could observe in our models suggest a need for evaluating increasing nanoplastic contaminants on Parkinson’s disease and dementia risk and progression,” West said.

“The technology needed to monitor nanoplastics is still at the earliest possible stages and not ready yet to answer all the questions we have,” he said.

Source: Duke University Medical Center

Study Discovers a New Driver of Brain Haemorrhage Formation

Source: CC0

A recent study has revealed a new culprit in the formation of brain haemorrhages that does not involve injury to the blood vessels, as previously believed. In the first-of-its kind study, researchers led by the University of California, Irvine discovered that interactions between aged red blood cells and brain capillaries can lead to cerebral microbleeds, offering deeper insights into how they occur and identifying potential new therapeutic targets for treatment and prevention.

The findings, published in the Journal of Neuroinflammation, describe how the team was able to watch the process by which red blood cells stall in the brain capillaries and then observe how the haemorrhage happens.

Cerebral microbleeds are associated with a variety of conditions that occur at higher rates in older adults, including hypertension, Alzheimer’s disease and ischaemic stroke.

“We have previously explored this issue in cell culture systems, but our current study is significant in expanding our understanding of the mechanism by which cerebral microbleeds develop,” said co-corresponding author Dr Mark Fisher, professor of neurology in UCI’s School of Medicine.

“Our findings may have profound clinical implications, as we identified a link between red blood cell damage and cerebral haemorrhages that occurs at the capillary level.”

The team exposed red blood cells to a chemical called tert-butyl hydroperoxide that caused oxidative stress; the cells were then marked with a fluorescent label and injected into mice.

Using two different methods, the researchers observed the red blood cells getting stuck in the brain capillaries and then being cleared out in a process called endothelial erythrophagocytosis.

As they moved out of the capillaries, microglia inflammatory cells engulfed the red blood cells, which led to the formation of a brain haemorrhage.

“It has always been assumed that in order for cerebral haemorrhage to occur, blood vessels need to be injured or disrupted. We found that increased red blood cell interactions with the brain capillaries represent an alternative source of development,” said co-corresponding author Xiangmin Xu, UCI professor of anatomy & neurobiology and director of the campus’s Center for Neural Circuit Mapping.

“We need to examine in detail the regulation of brain capillary clearance and also analyse how that process may be related to insufficient blood supply and ischaemic stroke, which is the most common form of stroke, to help advance the development of targeted treatments.”

Source: University of California – Irvine

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

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

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

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

Finding the Right Treatment for Controlling Parkinson’s Symptoms

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Finding the right medication regimen to treat Parkinson’s disease (PD) is a complex healthcare challenge. Wearable health trackers provide detailed information on patients’ symptoms, but this complex data is difficult to turn into useful treatment insights. Now, new research in the INFORMS journal Management Science shows that combining wearable health tracker data with state-of-the-art algorithms results in promising treatment strategies that could improve PD patients’ outcomes.

“Our model identified a Parkinson’s disease medication strategy: Frequent dosing of a slow-release medication formulation that would benefit almost all patients,” says Matt Baucum of Florida State University, one of the study authors.

“In fact, our model uses wearable sensors to predict that patients would spend almost twice as long each day (82% longer) with well-managed symptoms under our recommended medication strategy, compared with their existing medication regimens.”

The paper suggests the resulting models can offer novel clinical insights and medication strategies that can potentially democratise access to improved care.

“Our research suggests that combining rich data from wearable health trackers with the pattern-discovery capabilities of machine learning can uncover treatment strategies that otherwise might have gone underutilized,” says Anahita Khojandi, study co-author from the University of Tennessee, Knoxville.

“The algorithms we developed can even be used to predict patients who might benefit from more advanced PD therapies, which really highlights their ability to extract the maximum value from wearable data.”

Baucum and Khojandi, alongside fellow authors Dr Rama Vasudevan of Oak Ridge National Laboratory and Dr Ritesh Ramdhani a neurologist at Hofstra/ Northwell, emphasise that this work is ground-breaking for PD patients who may experience improved symptom control through continuous sensor monitoring and a novel AI approach.

Source: Institute for Operations Research and the Management Sciences

Keeping Cardiovascular Risk in Check Safeguards against Dementia

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

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.”