A new way to treat or prevent Alzheimer’s disease?

via National Institute on Aging

NIH-funded study identifies gene variant as potential drug target

Defying the odds, an individual at high risk for early-onset Alzheimer’s disease remained dementia-free for many years beyond what was anticipated. A study funded in part by the National Institute on Aging (NIA), part of the National Institutes of Health, led researchers to suggest that a gene variant may be the key, perhaps providing a new direction toward developing a treatment.

The research focused on the case of a woman who carried a gene mutation known to cause early-onset Alzheimer’s. However, she did not develop signs of the disease until her seventies, nearly three decades after her expected age of onset. The researchers suspect that she may have been protected because in addition to the gene mutation causing early-onset Alzheimer’s in her family, she also had two copies of the APOE3 Christchurch (APOE3ch) gene variant. Findings of this case study as published in Nature Medicine suggest that two copies of the APOE3ch variant, named after Christchurch, New Zealand where it was first identified, may protect against Alzheimer’s.

“Sometimes close analysis of a single case can lead to discovery that could have broad implications for the field,” said NIA Director Richard J. Hodes, M.D. “We are encouraged that as part of our wide array of studies, this research in the unique genetic makeup of an exceptional individual can reveal helpful information.”

Early-onset Alzheimer’s disease is rare, representing less than 10% of all people who have Alzheimer’s. It typically occurs between a person’s 30s to mid-60s. Risk for both early- and late-onset Alzheimer’s disease is affected by genetic factors.

For the study, researchers led by investigators at Massachusetts General Hospital, Boston, in collaboration with the University of Antioquia, Medellin, Colombia, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, and Banner Alzheimer’s Institute, Phoenix, looked at genetic data from a Colombian family with more than 6,000 living members. Family members who carry a rare gene mutation called Presenilin 1 (PSEN1E280A, have a 99.9% risk of developing early-onset Alzheimer’s disease.

The researchers confirmed that the woman in this case carried the PSEN1 E280A mutation, which caused early-onset Alzheimer’s in her other family members. However, she also had two copies of the APOE3ch gene variant, while no other affected family member carried two copies of this variant. Affected family members develop Alzheimer’s in their 40s, but she remained disease free until her 70s. Imaging tests showed that the woman had only minor neurodegeneration. She did have large amounts of amyloid protein deposits, a hallmark of Alzheimer’s disease, in her brain. But the amount of tau tangles, another hallmark of the disease, and the one more correlated with how thinking and memory are affected, was relatively low.

Experiments as part of the study showed that the APOE3ch variant may reduce the ability of APOE to bind to certain sugars called heparan sulphate proteoglycans (HSPG). APOE binding to HSPG has been implicated as one mechanism that may contribute to the amyloid and tau protein deposits that destroy the brain. The research suggests that a drug or gene therapy that could reduce APOE and HSPG binding has the potential to be a new way to treat or prevent Alzheimer’s disease.

Learn more: Unique case of disease resistance reveals possible Alzheimer’s treatment

 

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A new approach using 2 old drugs show promise for specific types of stroke and dementia

via Stroke Connection Magazine – American Stroke Association

Treatments that prevent recurrence of types of stroke and dementia caused by damage to small blood vessels in the brain have moved a step closer, following a small study.

The drugs – called cilostazol and isosorbide mononitrate – are already used to treat other conditions, such as heart disease and angina.

This is the first time they have been tested in the UK for the treatment of stroke or vascular dementia.

High tolerance

A study involving more than 50 stroke patients found that patients tolerated the drugs, with no serious side effects, even when the drugs were given in full dose or in combination with other medicines.

Experts say the findings pave the way for larger studies to check if the treatments can prevent brain damage and reduce risk of stroke and vascular dementia.

Damage to small blood vessels in the brain is responsible for around a quarter of strokes. It is also a common cause of memory problems and dementia.

Around 400,000 people in the UK are affected but there are no specific treatments. Currently the only way to reduce risk of the disease is by controlling blood pressure and cholesterol, stopping smoking and managing symptoms of diabetes.

Promising early signs

A team led by the Universities of Edinburgh and Nottingham recruited 57 patients who had experienced a stroke caused by damaged small blood vessels, known as a lacunar stroke.

Patients took the two medicines either individually or in combination for up to nine weeks, in addition to usual treatments aimed at preventing further strokes.

They completed health questionnaires and had regular blood pressure checks, blood tests and brain scans.

The findings suggest the drugs are safe for use in stroke patients, taken alone or in combination, at least in the short term.

There were also signs that the treatments helped improve blood vessel function in the arms and brain, and may improve thinking skills, but the researchers stress that further studies are needed to test this. A larger study, called LACI-2, is already underway.

Effective treatment

The study, published in EClinicalMedicine, was funded primarily by the Alzheimer’s Society, with support from the UK Stroke Association, British Heart Foundation, the European Union, National Institutes of Health Research, and NHS Research Scotland.

We are delighted that the results of this trial show promise for treating a common cause of stroke and the commonest cause of vascular dementia, since currently there are no effective treatments. Further trials are underway.

Professor Joanna Wardlaw Centre for Clinical Brain Sciences

There hasn’t been a new drug for dementia for 15 years, so finding evidence that these cheap existing drugs could prevent dementia after a stroke would be a huge breakthrough. It’s promising to see that these two drugs are safe to use and we’ll be excited to see the results of the next stage of testing in a couple of years, which will show whether these drugs can be an effective treatment.

Dr James PickettHead of Research at Alzheimer’s Society

Learn more: Drugs to prevent stroke and dementia show promise

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Robot helpers for the joy and sorrow of dementia

Undergraduate Alejandro E. Panduro (left), a cognitive science major, and postdoctoral researcher Hee Rin Lee, who focuses on computer science, work together with caregivers for people with dementia. (The caregivers’ faces have been pixelated to protect their anonymity.)
CREDIT
Healthcare Robotics Lab/University of California San Diego

Caregivers design robots that increase joyful moments and reduce emotional stress

Building robots that can help people with dementia has been a longtime goal for roboticists. Yet until now, no one has sought to survey informal caregivers, such as family members, about what characteristics and roles these robots should have.

A team of scientists at the University of California San Diego sought to address this by spending six months co-designing robots with family members, social workers, and other caregivers who care for people with dementia. They are presenting their findings at the Human Robot Interaction conference March 11 to 14 in South Korea.

Researchers found that caregivers wanted the robots to fulfill two major roles: support positive moments shared by caregivers and their loved ones; and lessen caregivers’ emotional stress by taking on difficult tasks, such as answering repeated questions and restricting unhealthy food.

“Caregivers conceived of robots not only managing difficult aspects of caregiving–but also for supporting joyful and fun activities,” said Laurel Riek, a professor of computer science at UC San Diego, and the paper’s senior author.

Spouses or adult children provide 75 percent of the care for people with dementia. That is equivalent to 15 million people in the United States alone, providing 18 billion hours of unpaid care per year with little support and few resources. Caregivers are also likely to overlook their own health and wellbeing, which can put both parties at risk.

Most technology designed to support caregivers only seeks to educate, rather than to reduce burden. Caregivers sometimes also have access to virtual support systems and connections to clinicians via smartphones or desktop computers, but again this focuses on education and not direct assistance.

By contrast, homecare robots could provide caregivers the respite they sorely need. Before building the robots, it is crucial to get caregivers’ input so that the robots are well designed and actually useful.

“It is imperative researchers take a community-health focused approach to understanding stakeholders’ perspectives prior to building the technology,” Riek said. “Especially in healthcare robotics – one should not walk in with a technology hammer.”

Half of the robots designed by caregivers were primarily focused on alleviating stress from the repetitive questions people with dementia ask. Caregivers also envisioned robots that could provide reminders of a person’s daily schedule and tasks. They also designed robots to help with physical therapy and manage medications.

As dementia progressed, caregivers wanted robots to interact more with the person with dementia by helping with daily tasks and offering reminders. The robots that caregivers imagined acted as counselors and facilitators–and sometimes as the “bad guys” who could say “no” to the person with dementia.

The researchers are now using these initial low-tech prototypes to build high-tech prototypes that they plan to begin testing in homes over the next year.

Interviews and hands-on workshops

For the study, researchers led by Riek built relationships with three different dementia day care centers in San Diego County.

A series of interviews and hands-on workshops with caregivers were conducted by two UC San Diego cognitive science undergraduate students, Sanika Moharana and Alejandro E. Panduro, and one computer science postdoc, Hee Rin Lee. A total of 18 people participated in the research, including 13 family members who acted as caregivers for people with various types of dementia, five social workers who led the day care centers, and three geriatric nursing students who work at the centers.

Based on everyone’s feedback, the team identified 16 major challenges that caregivers had to deal with, from difficulty accepting dementia, to isolation, to difficulty prioritizing self-care.

In the workshops, the researchers gave caregivers a brief presentation about the types of technologies available today, including pet-like robots, cleaning robots, telepresence robots, smart speakers and wearables.

Then, with the students’ help, caregivers selected key problems and collaboratively co-designed robots to tackle them. They used pre-cut foam shapes to build the robot prototypes. They also selected functions for the robots (such as playing games, reviewing photo albums, exercising, etc.) and a mode of interaction between the robot and person with dementia and caregivers (for example voice commands and touch screens).

Caregivers designed their ideal robots to follow predetermined scenarios supplied by researchers and the social workers, including preventing a person with dementia from driving, getting them to bathe, or answering repetitive questions.

Robot characteristics

Based on the results of the six-month long community design process, the researchers identified a number of characteristics and design guidelines for robots to support dementia caregivers and people with dementia:

  • Robots should help redirect conversations when repetitive questioning becomes burdensome
  • Robots should be integrated into everyday objects that the people with dementia are already familiar with, or borrow features from those objects. For example, one caregiver wanted her husband to get messages through the TV, which he spends a lot of time watching.
  • Robots should be able to adapt to new situations and to the behavior of the person with dementia. This is particularly important because dementia is a progressive disease and each stage brings new challenges for caregivers. In addition, patterns of progression vary from person to person and as a result are almost impossible to predict.
  • Robots should be able to learn from end users, and customize and personalize their interaction and responses.
  • Robots should have human-like components. That is not to say that they should look human. Rather the machines could, for example, use a real human voice or face. “When caregivers wanted robots to take active roles in persuading people with dementia to do something, they designed robots with more human-like features,” the researchers write. Related to this, caregivers wanted robots to include features that would help build trust, such as looking like a friend or clinician.
  • Robots should interact with humans via voice activation –much like a smart speaker. More specifically, caregivers wanted the robots to use voices that their loved ones would be familiar with–caregivers or doctors. Caregivers also wanted robots to be capable of facial recognition.

Learn more: The robots that dementia caregivers want: Robots for joy, robots for sorrow

 

 

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Could readily available plant-based supplements offer protection against dementia?

USC researchers are studying plant-derived substances, like green tea, that inhibit production of the sticky amyloid beta plaques known to cause Alzheimer‘s disease. (Photo/Pixabay)

The findings — focused on components contained in green tea and carrots — lend credence to the idea that certain readily available, plant-based supplements might offer protection against dementia in people.

A diet containing compounds found in green tea and carrots reversed Alzheimer’s-like symptoms in mice genetically programmed to develop the disease, USC researchers say.

Researchers emphasize that the study, published in the Journal of Biological Chemistry, was in mice, and many mouse discoveries never translate into human treatments. Nevertheless, the findings lend credence to the idea that certain readily available, plant-based supplements might offer protection against dementia in humans.

“You don’t have to wait 10 to 12 years for a designer drug to make it to market; you can make these dietary changes today,” said senior author Terrence Town, a professor of physiology and neuroscience at the Keck School of Medicine of USC’s Zilkha Neurogenetic Institute. “I find that very encouraging.”

Diet and Alzheimer’s: Combination therapy

What’s more, the study supports the idea that combination therapy, rather than a single magic bullet, may offer the best approach to treating the 5.7 million Americans living with Alzheimer’s. Combination treatment is already the standard of care for diseases such as cancer, HIV infection and rheumatoid arthritis.

For this study, the researchers took a look at two compounds, EGCG, or epigallocatechin-3-gallate, a key ingredient in green tea, and FA, or ferulic acid, which is found in carrots, tomatoes, rice, wheat and oats.

The researchers randomly assigned 32 mice with Alzheimer’s-like symptoms to one of four groups with an equal number of males and females. For comparison, each group also included an equal number of healthy mice. For three months, the mice consumed a combination of EGCG and FA, or EGCG or FA only, or a placebo. The dosage was 30 milligrams per kilogram of body weight — a dosage well-tolerated by humans and easily consumed as part of a healthy diet.

Diet and Alzheimer’s: Testing results

Before and after the three-month special diet, scientists ran the mice through a battery of neuropsychological tests that are roughly analogous to the thinking and memory tests that assess dementia in humans. Of particular note was a maze in the shape of a Y, which tests a mouse’s spatial working memory — a skill that humans use to find their way out of a building.

Healthy mice instinctively explore each arm of the Y maze, looking for food or a route to escape and entering the three arms in sequence more often than by chance alone. Impaired mice can’t do this as well as their mentally healthy counterparts.

“After three months, combination treatment completely restored spatial working memory and the Alzheimer’s mice performed just as well as the healthy comparison mice,” Town said.

How did it work? Town says one mechanism appeared to be the substances’ ability to prevent amyloid precursor proteins from breaking up into the smaller proteins called amyloid beta that gum up Alzheimer patients’ brains. In addition, the compounds appeared to reduce neuroinflammation and oxidative stress in the brain—key aspects of Alzheimer’s pathology in humans.

Town said he and his lab will continue exploring combination treatment, with a focus on plant-derived substances that inhibit production of the sticky amyloid beta plaques.

Learn more: Diet reverses Alzheimer’s-like symptoms in lab model

 

 

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Using ultrasound to delay the effects of dementia

UQ’s Professor Jurgen Gotz, chairman of the Clem Jones Centre for Ageing Dementia Research

Safety testing of a pioneering ultrasound technique that could delay the effects of dementia will begin in Brisbane late next year, led by University of Queensland researchers.

Federal Minister for Health Greg Hunt MP has announced $10 million in funding, which along with philanthropic donations brings UQ closer to its $30 million goal to commence clinical trials and further progress the associated research.

The phase 1 trial involving a small number of patients will explore whether the  technique developed at UQ’s Queensland Brain Institute (QBI) in 2015 is safe to use in the fight against the degenerative condition.

UQ QBI Director Professor Pankaj Sah said government and philanthropic funding would help researchers accelerate the development of the technique, understand the underlying mechanisms and how it might be used to more effectively treat dementia.

“The technology temporarily opens the blood-brain-barrier to remove toxic plaques from the brain and has successfully reversed Alzheimer’s symptoms and restored memory function in animal models,” Professor Sah said.

“The human safety trials late next year are the next step, representing an investment in research that is already underway.

“Funding is essential if we are to continue to move closer to producing a non-invasive treatment for dementia, which affects more than 350,000 people nationwide.”

Without a medical breakthrough, the number of Australians living with the disease is expected to increase to almost 1.1 million by 2056, bringing the cost of hospitalisation, care and lost productivity to more than $1 trillion.

UQ Vice-Chancellor and President Professor Peter Høj said urgent action for dementia was critical.

“We are thrilled to see Federal and State Governments partner with philanthropists and UQ to advance this important work,” he said.

“We must continue to build capacity in the dementia research sector by supporting students and early career dementia researchers.

“This funding will ensure we keep some of the world’s brightest minds focused on finding a cure for dementia, here in Brisbane.”

Learn more: New funding takes UQ towards clinical trials of dementia ultrasound treatment

 

 

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