Caregiving, International Policies, Research & Best Practice

Why a drug treatment for dementia has eluded us

Posted on January 12, 2018January 12, 2018 by Joanna Sun

File 20180109 83553 1tp4671.jpg?ixlib=rb 1.1

Have our hopes of a drug treatment for dementia been dashed by drug company Pfizer giving up on research efforts?
from http://www.shutterstock.com

Jürgen Götz, The University of Queensland

Finding a cure for neurodegenerative diseases such as Alzheimer’s is challenging. They’re difficult to diagnose, and drugs struggle to get into the brain as the brain’s blood supply is largely separate to the rest of the body. Not surprisingly, several companies have left this territory in recent years. This week, pharmaceutical giant Pfizer announced it will stop research into developing drugs to treat Alzheimer’s disease, after costly failed attempts over the past decade.

In recent years some clinical trials involving potential dementia drugs have had disappointing setbacks. In 2012, Pfizer and Johnson & Johnson halted development of the antibody drug bapineuzumab, after it failed in late-stage trials to treat patients with mild to moderate Alzheimer’s.

Despite this week’s announcement, Pfizer’s support of the UK’s Dementia Discovery Fund, an initiative involving the government, major pharmaceutical companies, and Alzheimer’s Research UK, may be where their money can make the most impact in this space. The fund aims to boost dementia research investment by financing early-stage drug development projects. And other pharma companies, such as Eli Lilly, Biogen and Novartis have continued to pursue dementia drug development with modest but promising success to date.

So what makes dementia such a difficult condition to treat with drugs, and is progress being made towards a treatment?

Why dementia is so hard to treat

Despite the vast number of people affected globally, with an estimated 46.8 million people currently living with dementia, there is currently no cure. While current treatments manage symptoms (the latest drug to gain FDA approval was memantine, in 2003) they offer no prospect of recovery.

Part of the difficulty in finding treatments for dementia stems from the fact it’s not a single disease, but a complex health problem with more than 50 underlying causes. Dementia can be better thought of as an umbrella term describing a range of conditions that cause parts of the brain to deteriorate progressively.

Most drug treatments currently in development have targeted the pathology of Alzheimer’s disease, the most common form of dementia, which accounts for about 60 to 70% of all cases.

Finding a successful treatment for Alzheimer’s faces two major hurdles: the first being we still don’t know enough about the disease’s underlying biology. For example, we don’t know what exactly regulates the toxic build-up of amyloid-β plaques and tau tangles in the brain that are found in Alzheimer’s patients, which specific types of these are toxic, or why the disease progresses at different rates in different people.

It doesn’t help that symptoms of Alzheimer’s develop gradually and slowly and a diagnosis might only be made years after the brain has started to undergo neurodegenerative changes. To boot, it’s not uncommon for Alzheimer’s to be present as well as other forms of dementia.

The second major hurdle to finding a treatment is that drugs need to first cross the blood-brain barrier. The blood–brain barrier provides a defence against disease-causing pathogens and toxins that may be present in our blood, and by design exists to keep out foreign substances from the brain. The downside is that it also keeps the vast majority of potential drug treatments from reaching the brain.

The brain has a blood barrier that protects it from pathogens that invade the rest of our body, which also means drugs can’t get in there.
from http://www.shutterstock.com

Promising steps in the right direction

Currently available medications such as those which block the actions of an enzyme that destroys an important chemical messenger in the brain for memory (acetylcholinesterase inhibitors) or blocks the toxic effects of another messenger, glutamate (memantine) temporarily manage symptoms. But new treatments are focused on slowing or reversing the disease process itself, by targeting the underlying biology.

One approach, called immunotherapy, involves creating antibodies that bind to abnormal developments in the brain (such as amyloid-β or tau), and mark them for destruction by a range of mechanisms. Immunotherapy is experiencing a surge of interest and a number of clinical trials – targeting both amyloid-β and tau – are currently underway.

Aducanumab, an antibody targeting amyloid-β, has shown promise in clinical trials and phase 3 trials are currently ongoing, as are several tau-based strategies. If any are successful, we would have a vaccine for Alzheimer’s.

It’s estimated only 0.1% of antibodies circulating in the bloodstream enter the brain – this also includes the therapeutic antibodies currently used in clinical trials. An approach my team is taking is to use ultrasound to temporarily open the blood-brain barrier, which increases the uptake of Alzheimer’s drugs or antibody fragments.

We’ve had success in mice, finding ultrasound can clear toxic tau protein clumps, and that combining ultrasound with an antibody fragment treatment is more effective than either treatment alone in removing tau and reducing Alzheimer’s symptoms. The next challenge will be translating this success into human clinical trials.

The task of dementia drug development is no easy feat, and requires collaboration across government, industry and academia. In Australia, the National Dementia Network serves this purpose well. It’s only through perseverance and continued investment in research that we’ll one day have a treatment for dementia.

With thanks to Queensland Brain Institute Science Writer Donna Lu.

Jürgen Götz, Director, Clem Jones Centre for Ageing Dementia Research, The University of Queensland

This article was originally published on The Conversation. Read the original article.

Caregiving, Research & Best Practice, The Built Environment

How the brain selectively remembers new places

Posted on January 7, 2018January 7, 2018 by Joanna Sun

25 DECEMBER 2017 | Neuroscientists identify a circuit that helps the brain record memories of new locations.

MIT News release – Source: How the brain selectively remembers new places

When you enter a room, your brain is bombarded with sensory information. If the room is a place you know well, most of this information is already stored in long-term memory. However, if the room is unfamiliar to you, your brain creates a new memory of it almost immediately.

MIT neuroscientists have now discovered how this occurs. A small region of the brainstem, known as the locus coeruleus, is activated in response to novel sensory stimuli, and this activity triggers the release of a flood of dopamine into a certain region of the hippocampus to store a memory of the new location.

“We have the remarkable ability to memorize some specific features of an experience in an entirely new environment, and such ability is crucial for our adaptation to the constantly changing world,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and director of the RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory.

“This study opens an exciting avenue of research into the circuit mechanism by which behaviorally relevant stimuli are specifically encoded into long-term memory, ensuring that important stimuli are stored preferentially over incidental ones,” adds Tonegawa, the senior author of the study.

Akiko Wagatsuma, a former MIT research scientist, is the lead author of the study, which appears in the Proceedings of the National Academy of Sciences the week of Dec. 25.

New places

In a study published about 15 years ago, Tonegawa’s lab found that a part of the hippocampus called the CA3 is responsible for forming memories of novel environments. They hypothesized that the CA3 receives a signal from another part of the brain when a novel place is encountered, stimulating memory formation.

They believed this signal to be carried by chemicals known as neuromodulators, which influence neuronal activity. The CA3 receives neuromodulators from both the locus coeruleus (LC) and a region called the ventral tegmental area (VTA), which is a key part of the brain’s reward circuitry. The researchers decided to focus on the LC because it has been shown to project to the CA3 extensively and to respond to novelty, among many other functions.

The LC responds to an array of sensory input, including visual information as well as sound and odor, then sends information on to other brain areas, including the CA3. To uncover the role of LC-CA3 communication, the researchers genetically engineered mice so that they could block the neuronal activity between those regions by shining light on neurons that form the connection.

To test the mice’s ability to form new memories, the researchers placed the mice in a large open space that they had never seen before. The next day, they placed them in the same space again. Mice whose LC-CA3 connections were not disrupted spent much less time exploring the space on the second day, because the environment was already familiar to them. However, when the researchers interfered with the LC-CA3 connection during the first exposure to the space, the mice explored the area on the second day just as much as they had on the first. This suggests that they were unable to form a memory of the new environment.

The LC appears to exert this effect by releasing the neuromodulator dopamine into the CA3 region, which was surprising because the LC is known to be a major source of norepinephrine to the hippocampus. The researchers believe that this influx of dopamine helps to boost CA3’s ability to strengthen synapses and form a memory of the new location.

They found that this mechanism was not required for other types of memory, such as memories of fearful events, but appears to be specific to memory of new environments. The connections between the LC and CA3 are necessary for long-term spatial memories to form in CA3.

“The selectivity of successful memory formation has long been a puzzle,” says Richard Morris, a professor of neuroscience at the University of Edinburgh, who was not involved in the research. “This study goes a long way toward identifying the brain mechanisms of this process. Activity in the pathway between the locus coeruleus and CA3 occurs most strongly during novelty, and it seems that activity fixes the representations of everyday experience, helping to register and retain what’s been happening and where we’ve been.”

Choosing to remember

This mechanism likely evolved as a way to help animals survive, allowing them to remember new environments without wasting brainpower on recording places that are already familiar, the researchers say.

“When we are exposed to sensory information, we unconsciously choose what to memorize. For an animal’s survival, certain things are necessary to be remembered, and other things, familiar things, probably can be forgotten,” Wagatsuma says.

Still unknown is how the LC recognizes that an environment is new. The researchers hypothesize that some part of the brain is able to compare new environments with stored memories or with expectations of the environment, but more studies are needed to explore how this might happen.

“That’s the next big question,” Tonegawa says. “Hopefully new technology will help to resolve that.”

The research was funded by the RIKEN Brain Science Institute, the Howard Hughes Medical Institute, and the JPB Foundation.

Caregiving, Research & Best Practice, The Built Environment

Architecture And Design Help the Brain to Recover

Posted on December 19, 2017December 19, 2017 by Joanna Sun

How does the hospital environment affect our rehabilitation? New research from the University of Gothenburg, Sweden, into how the space around us affects the brain reveals that well-planned architecture, design and sensory stimulation increase patients’ ability to recover both physically and mentally. Digital textiles and multisensory spaces can make rehabilitation more effective and reduce the amount of time spent in care.

In an interdisciplinary research project, Kristina Sahlqvist has used research into the recovery of the brain to examine how hospitals can create better environments for rehabilitation.

“We want to help patients to get involved in their rehabilitation, a side effect of which can be an improvement in self-confidence,” says Sahlqvist, interior architect and researcher at the University of Gothenburg’s School of Design and Crafts (HDK).

The project drew on all the expertise used on a ward, with input from neurologists, rehabilitation doctors, nurses, psychologists, occupational therapists and physiotherapists. The result is a conceptual solution for an optimal rehabilitation ward.

“Our concept gives the ward a spatial heart, for example, where patients and their families can prepare food and eat together, which allows for a more normal way of spending time together in a hospital environment,” says Sahlqvist.

In tandem with her research work, she has teamed up with a designer and researcher at the Swedish School of Textiles in Borås on an artistic development project where they redesigned furniture, developed easy-grip cups and cutlery and used smart textiles, in other words textiles with technology embedded in them. The concept includes a table and chairs, a rug and a muff with integral heating, a cardigan with speakers and a soft bracelet that is also a remote control.

In order to measure and test the research theories Sahlgrenska University Hospital will be developing an intensive care room featuring multimodal stimulation, where all the senses are affected. The work involves an architect, doctors, hospital staff, musicians, a designer, an acoustician and a cognition specialist. In a bid to see what kind of results the environment can produce in practice, the researchers will take account of the entire social situation of patients, family and staff.

There are other interesting tricks in the field of neuroarchitecture, where it is possible, for example, to use spatial expressions to improve learning. Although these are currently used predominantly in schools, they could also have potential for the elderly.

“It’s worth wondering why there are so many educational models for preschool children but so few for the elderly. Many old people need a far more stimulating environment than they have at the moment,” says Sahlqvist.

Date: November 3, 2011

Source: University of Gothenburg

Release from University of Gothenburg

建筑和设计帮助大脑恢复

发布日期：2011年11月2日。
哥德堡大学发布

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医院环境如何影响我们的康复？瑞典哥德堡大学的最新研究发现，我们周围的空间如何影响大脑，显示出精心策划的建筑，设计和感官刺激可以提高患者身心恢复的能力。数字纺织品和多感官空间可以使康复更有效，并减少花费在护理上的时间。

在一个跨学科研究项目中，Kristina Sahlqvist利用大脑恢复研究来研究医院如何创造更好的康复环境。

哥德堡大学设计与工艺学院（HDK）室内设计师兼研究员Sahlqvist说：“我们希望帮助患者参与康复治疗，其副作用可以提高自信心。

该项目利用了病房的所有专业知识，由神经科医生，康复医生，护士，心理学家，职业治疗师和物理治疗师提供投入。结果是最佳康复病房的概念性解决方案。

Sahlqvist说：“我们的理念给病房提供了一个空间的心脏，例如，病人和他们的家人可以一起准备食物和一起吃饭，这样可以在医院环境中更加正常地花时间在一起。

在她的研究工作的同时，她与布罗斯的瑞典纺织学院的一位设计师和研究员合作开展了一个艺术发展项目，重新设计了家具，开发了易握杯子和餐具，并使用了智能纺织品，换句话说纺织品其中嵌入了技术。这个概念包括一张桌子和椅子，一个地毯和一个带有整体加热装置的手套，一个带扬声器的开襟衫和一个也是遥控器的软手镯。

为了衡量和测试研究理论，萨尔格林斯卡大学医院将开发一个以多模式刺激为特征的重症监护室，所有感官都受到影响。这项工作涉及建筑师，医生，医院工作人员，音乐家，设计师，声学家和认知专家。为了研究环境在实践中能产生怎样的结果，研究人员将考虑患者，家属和工作人员的整个社会状况。

在神经体系结构领域还有其他一些有趣的技巧，例如使用空间表达来改善学习。虽然这些目前主要用于学校，但也可能对老年人有潜力。

Sahlqvist表示：“值得一提的是，为什么学龄前儿童的教育模式如此之多，而老年人的教育模式却很少。许多老年人需要的环境比现在更为刺激。

Caregiving, Research & Best Practice, The Built Environment, Therapeutic Activities

Alarming amounts of noise demand ways to silence noisy hospital environments

Posted on December 12, 2017December 11, 2017 by Joanna Sun

Spending a night in the hospital is not only stressful, but also loud. The constant beeps, whirrs and alarms ascend to a cacophony that produces anything but a relaxing, restful environment. Researchers will summarize the limited number of studies available on hospital noise and discuss the different approaches health care facilities are taking to bring restful repose to patients across the country during the 174th ASA Meeting, Dec. 4-8, 2017, in New Orleans, La.

Source: Alarming amounts of noise demand ways to silence noisy hospital environments

Hospital noise is a growing concern for patients, family and staff, but many facilities are looking for new approaches to reduce the din and bring peace back to their environment.

Public Release: ACOUSTICAL SOCIETY OF AMERICA

WASHINGTON, D.C. December 6, 2017– Spending a night in the hospital is not only stressful, but also loud. The constant beeps, whirrs and alarms ascend to a cacophony that produces anything but a relaxing, restful environment. Ilene Busch-Vishniac, of BeoGrin Consulting in Baltimore, Maryland, will summarize the limited number of studies available on hospital noise and discuss the different approaches health care facilities are taking to bring restful repose to patients across the country.

According to the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, noise is the top complaint of patients, staff and visitors. “Nearly everyone has a stay in a hospital at some point,” Busch-Vishniac said. “Noise is a universal problem in hospitals around the world.”

Busch-Vishniac will explore these concepts during the 174th Meeting of the Acoustical Society of America, being held Dec. 4-8, 2017, in New Orleans, Louisiana. Noises emanate from a variety of sources at the bedside. Airflow and the noisy machines controlling it are kept on high to prevent pathogens from lingering near patients, and overhead pages alert staff of needs or announcements. Equipment alarms are the most egregious source, and although they are designed to alert staff of changes in the patient’s medical condition, many also sound when medication needs to be changed or when battery conditions are low.

“Alarms in hospitals are being horribly abused,” Busch-Vishniac said. “Most of the time, they don’t in fact indicate urgent situations.”

Previous studies showed that alarms at a patient’s bedside sound an average 133 times per day. With so many alarms, staff often face alarm fatigue as well.

“Most alarms are being responded to eventually, but not all in a timely fashion,” said Busch-Vishniac. “Staff also may not respond quickly because they recognize that the sound is not critical and the situation will right itself.”

Besides the obvious barrier to rest, high noise levels have been associated with changes in the patient’s heart rate, respiration and blood pressure. These changes increase stress levels and may impair healing. The noise can also impair communication between patients and staff.

With noise levels on the rise, the Centers for Medicare and Medicaid Services (CMS) initiated the HCAHPS survey in 2008 to assess consumer perception of health care providers and systems. Today, more than 5,500 hospitals contribute to the report, which consists of patients’ responses on seven composite measures, including questions focused on room cleanliness and quietness.

The survey has teeth. Hospital value-based purchasing links up to 30 percent of CMS payments to hospitals across the country to the results of the survey.

“Faced with a loss of money, many hospitals are looking for ways to address noise levels in a way that patients can see as an improvement,” said Busch-Vishniac.

Hospitals have been developing and implementing noise control programs that can be broken into two categories: engineering and administrative interventions.

Engineering interventions aim to find ways to quiet the room. The solutions can be as simple as closing the door to a patient’s room or as complex as installing acoustical absorption materials along the walls and ceiling to dampen the noise level. Administrative interventions focus on changing behaviors. Many hospitals have instituted quiet hours when doors are closed and voices are kept low.

One of the big changes during the past 10 years has shifted alarms from solely sounding at the patient’s bedside to also alerting a central monitor at the nursing station. This approach improves the ability of staff to identify and respond to alarms set at a reduced volume.

According to Busch-Vishniac, it may be possible in the future to remove alarms from the bedside. A quiet hospital may not be a pipedream for much longer.

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Presentation 3pIDa: “Hospital noise: how bad is it?” by Ilene Busch-Vishniac is at 1:45-2:05 p.m. CST, Wednesday, Dec. 6, 2017, in Salon E in the New Orleans Marriott. https://asa2017fall.abstractcentral.com/s/u/M8hKSrQu66E

Caregiving, Dementia, Research & Best Practice, The Built Environment, Therapeutic Activities

A study shows that 1 truly remarkable change can improve lives and help save cost in residential care homes!

Posted on July 19, 2017July 20, 2017 by Joanna Sun

In residential aged care, how many times have you heard the howls of frustrations as management and staff, shake their fist in the air, bicker and scratch their heads to work out how to improve dementia care at the same time balance the books. It’s a constant frustration, not just for the staff but for the residents with dementia and caregivers as well as they continue to pay for care and feel that they are unheard, unseen and their needs have gone unnoticed.

Good news, the latest study was presented at the Alzheimer’s Association International Conference from the University of Exeter and carried out in collaboration with University College London, Hull, Bangor and Alzheimer’s Society UK. The study evidently highlighted the fact that activities carried out in line with the philosophy of Person-Centred Care, coupled with a week of social activities resulted in a reduced in responsive behaviours in dementia and improve the quality of life for residents with dementia in a residential care home.

The large scale study funded by the National Institute for Health Research was carried out in 69 residential care homes in the United Kingdom and consisted of 800 residents with dementia. Each of the 69 residential care home had two staff attend a four-day session, training them to socially engage with residents with dementia and finding out what residents would like in the areas of their care needs. When executed, this person-centred care approach coupled with an hour of social engagement found that not only was there a reported in the increase in quality of life but a reduction in responsive behaviours of dementia resulting in cost savings in dementia care to the organisation compared to care without such interventions.

“Taking a person-centred approach is about really getting to know the resident as an individual – knowing their interests and talking with them while you provide all aspects of care. It can make a massive difference to the person themselves and their carers. We’ve shown that this approach significantly improves lives, reduces agitation and actually saves money too. This training must now be rolled out nationwide so other people can benefit.”

-Dr Jane Fossey ( Oxford Health NHS Foundation Trust)

With the success of this study, the researchers are potentially aiming to have this intervention carried out in 28,000 residential care homes in the country, potentially positively impacting up to 300,000 residents with dementia.

Caregiving, Research & Best Practice, Therapeutic Activities

The Lantern Project Australia

Posted on May 25, 2017 by Joanna Sun

The Lantern Project Australia, founded by Cherie Hugo, is about giving aged care residents the quality of life they deserve through good food and nutrition.

Source: The Lantern Project Australia