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Landmark breakthrough in understanding Alzheimer’s

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Brain cells vulnerable to Alzheimer’s Disease have been identified for the first time, in a breakthrough scientists hope could lead to targeted treatments to boost the brain’s resilience.

It has so far remained unknown in Alzheimer’s research why some brain cells succumb to the disease years before symptoms first appear, while others seem unaffected by the degeneration surrounding them until the disease’s final stages.

Now, in a groundbreaking study, the neurons that are among the first victims of the disease –  accumulating toxic ‘tangles’ and dying off earlier than neighbouring cells – have been identified for the first time.

“We know which neurons are first to die in other neurodegenerative diseases like Parkinson’s disease and ALS, but not Alzheimer’s,” says co-senior author Martin Kampmann, associate professor in the UCSF Institute for Neurodegenerative Diseases.

“If we understood why these neurons are so vulnerable, maybe we could identify interventions that could make them, and the brain as a whole, more resilient to the disease.”

Alzheimer’s researchers have long studied why certain cells are more prone to producing the toxic tangles of the protein known as tau, whose spread through the brain drives widespread cell death and resulting progressive memory loss, dementia, and other symptoms.

But researchers have not looked closely at whether all cells are equally vulnerable to the toxic effects of these protein accumulations.

“The belief in the field has been that once these trash proteins are there, it’s always ‘game over’ for the cell, but our lab has been finding that that is not the case,” said Lea Grinberg, senior co-author and associate professor in the UCSF Memory and Ageing Centre.

“Some cells end up with high levels of tau tangles well into the progression of the disease, but for some reason don’t die.

“It has become a pressing question for us to understand the specific factors that make some cells selectively vulnerable to Alzheimer’s pathology, while other cells appear able to resist it for years, if not decades.”

To identify selectively vulnerable neurons, the researchers studied brain tissue from people who had died at different stages of Alzheimer’s disease, obtained from the UCSF Neurodegenerative Disease Brain Bank and the Brazilian BioBank for Ageing Studies.

The São Paulo-based biobank collects tissue samples from a broad population of deceased individuals, including many without a neurological diagnosis whose brains nevertheless show signs of very early-stage neurodegenerative disease, which is otherwise very difficult to study in humans.

The team studied tissue from ten donor brains using a technique called single-nucleus RNA sequencing, which let them group neurons based on patterns of gene activity.

In a brain region called the entorhinal cortex, one of the first areas attacked by Alzheimer’s, the researchers identified a particular subset of neurons that began to disappear very early on in the disease.

Later in the course of the disease, the researchers found, a similar group of neurons were also first to die off when degeneration reached the brain’s superior frontal gyrus.

“These findings support the view that tau buildup is a critical driver of neurodegeneration, but we also know from other data from the that not every cell that builds up these aggregates is equally susceptible,” adds researcher Kun Leng.

“Our discovery of a molecular identifier for these selectively vulnerable cells gives us the opportunity to study in detail exactly why they succumb to tau pathology, and what could be done to make them more resilient.

“This would be a totally new and much more targeted approach to developing therapies to slow or prevent the spread of Alzheimer’s disease.”

Case management

‘Yes we can, bring it on’

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Louise Sheffield - founder of Active Case Management

Ten years ago, Louise Sheffield established Active Case Management, despite having no background in case management. Here, she reflects on the growth of the company in terms of size, reach and reputation and how they are entering their second decade with positivity.

“Very refreshing but completely terrifying.”

Louise Sheffield’s early experience of setting up on her own in case management was a far cry from her career to date.

“I’d worked in the NHS and at the time there weren’t many people doing the work I did,” reflects Louise, whose background is in occupational therapy specialising in brain injury.

“But then here I was setting up a business in this new area of case management – I’d never been a case manager, although my service co-ordinator role in the NHS had drawn on the same skills of assessment and planning through a multi-disciplinary rehabilitation programme.

“I’d gone from being in the NHS and knowing everyone at every event I went to, to going to events as a case manager and knowing no-one.

“It was a strange time at first, and I did think I must’ve been mad. But my instinct then was the same as it is now – just to crack on.”

And the determination of Louise – with her years of experience as an NHS rehabilitation co-ordinator – to make her mark has paid off, with her business, Active Case Management, marking its 10th anniversary.

With a team of 13 people covering the Midlands, North West and North East from its Wigan head office, its reach continues to grow.

“For the first few years it was only me and it was a learning process in many ways, but I wanted to learn, I was starting with a blank slate,” says Louise.

“It was a very different mentality to working in the NHS. While I was there, we were very conscious of waiting lists and our targets and whether a different service was more appropriate than ours. I was the gatekeeper of the service – but for me, from the outset with my business, it was a case of I’ll take on any client, as long as it’s within my capability.

“I didn’t always know if I was doing things right, but the solicitors seemed to be happy, the clients were happy, so I thought it must be right.

“But as you grow and create relationships and build a team, you find you have the benefit of the expertise and experience of those around you. That continues to help me.”

Having built a strong reputation for its support of, and dedication to, clients, Active is also known for its intermediary work.

Louise herself is a registered intermediary, a role she has now established as her niche in case management, but was something she was unsure how to incorporate into Active’s offering in the early days.

“I actually saw it as a potential threat to my case management work at first – I’m always cautious if someone claims to be an expert in too many things,” says Louise.

“But actually, I needn’t have been so conscious of that, as it’s become something we’re now known for and I’m very proud of our reputation.

“My favourite kind of client is one who is a bit cheeky, bit naughty, who maybe sails a bit close to the wind. There will be some challenging behaviour alongside the bags of character – but that often comes with disinhibition and impulsiveness and that can often get people into trouble with the law.

“And that is where our specialism can be really important.”

While fulfilling both roles concurrently, case manager and intermediary work are very different, says Louise.

“If I put all my files together for my case management work, they would fill an entire wall of the office, whereas my intermediary work would fit into one filing cabinet,” she says.

“With case management, you learn a huge amount about your clients, and you’ll know their shoe size, you’ll know their aunty’s name, you’ll know that with some clients you’d better answer the phone to them at 2am or else they’ll have called another 10 times before 3am.

“But with intermediary work, it’s very narrow remit but very deep. I like how it doesn’t take up the huge amount of brain space you need for your clients and their lives.

“But the roles definitely complement each other and the skills you need for one do help you with the other.”

Going forward, Active continues to progress and Louise’s can-do attitude is at the heart of that.

“This was a different world at first, but it’s a great one to work in. I’ve got a great team of 13 people now and we’ll keep on doing the best we can for our clients,” she says.

And the ethos of the team as they enter their second decade is more determined than ever before.

“For us, it’s all about saying ‘Yes we can, bring it on’,” adds Louise.

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Case management

Pandemic has ‘significant impact’ on case management

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Case management company BABICM helped produce the report

The COVID-19 pandemic has had a “significant impact” on case management practice and the lives of those living with brain injuries, early findings of a UK-wide research project have revealed.

Last year, BABICM launched a study among its members to discover the true impact of the pandemic, and how case managers and clients alike are adapting to the ongoing restrictions.

The study has gathered the personal accounts of people with brain injuries across the country, and their support networks, to understand how lives and working practices have changed since March last year.

The project, which is being completed by BABICM and the University of Plymouth, has now moved into the focus group phase, which will explore the experiences of brain injury case managers.

Areas of interest include changes of practice, the impact on their clients, their families and support networks, and access to services.

While fact finding is still ongoing, with two of the five scheduled focus groups now completed, trends are already emerging.

“We have already noticed some interesting trends amongst the case managers – but what is becoming abundantly clear is that the COVID-19 pandemic has had a significant impact on case management practice and the lives of those who have sustained a brain injury,” says Ben Needham-Holmes, a member of the BABICM research subgroup who is spearheading the project.

“Our thanks go out to all of those who are taking part in this study. Without their participation, this study would not be possible.”

Following the culmination of the focus group phase, the project will then move into interviews with clients and/or their family members or support networks to learn about their experiences.

This is expected to conclude by May, after which time the data analysis will take place, which will draw out the key themes from the research.

The final research will be shared in academic and professional forums, to help shape future case management practice.

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Case management

‘I’m proud of how we have all pulled together’

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Telerehab has become the new normal since the pandemic

Case management has faced unprecedented challenges during the past year, which has seen it respond with positivity and agility to ensure service to its clients could be maintained. In the latest in our Q&A series, Sarah Cooke from Bush & Co shares her experiences, and how the newly-adopted telerehab will undoubtedly play a role going forward.

Can you summarise how the past few months have been for you

It’s certainly been the biggest challenge of my career! But I feel proud of how we have all pulled together, in whichever capacity we work with our clients, so they have been able to continue their rehabilitation.

How did you adapt to the restrictions of lockdown? Were you able to do this quickly or did it take a bit of time?

I adapted pretty quickly to the lockdown restrictions as I already worked remotely from home so my office space was set up. It was also normal to communicate with colleagues and clients by email and telephone. The strangest part was going from a quiet house to having my family at home either working from home or furloughed. I’m sure this affected the internet connection at times!

I think working within a supportive team has been really important. By supporting each other we have looked after each other’s well-being which, in turn, has enabled us to continue delivering a first class service to our clients. It is important to remember we are clinicians but also have personal lives and have been affected like everyone else.

At the beginning of lockdown the Bush & Co management team reacted quickly to the situation and put a Covid-19 risk assessment in place, supported us with increased communications and the relevant, latest guidance. This enabled me to decide how to complete Immediate Needs Assessments and reviews and ensured good communication with clients and stakeholders was maintained. We also put new initiatives in place quickly such as loaning out tablets to clients who had little or no access to technology. This meant Immediate Needs Assessments could be completed remotely but also meant ongoing case management could continue.

What have been the main challenges – were you able to overcome them? 

Initially the access to PPE caused a challenge. However for those clients that the Covid-19 risk assessment identified still needed home visits, Bush & Co were able to provide PPE packs for each visit. I think social media also helped at this time as I received additional face masks from LinkedIn connections who shared what they could spare.

At the beginning of the pandemic we were faced with how to keep our clients’ rehabilitation going. NHS departments had closed and important surgery cancelled. Plus service providers needed to convert to new ways of working. My main focus was preventing clients from deteriorating and enabling them to maintain during this period. This was where the stakeholders stepped in and ensured funds where available to support our clients. For example, one of my clients’ pain had increased so the stakeholders funded an electric profiling bed to keep her at home and comfortable whilst she waits for surgery. Another example is how the pandemic has hit a lot of our clients psychologically. The stakeholders have secured funding for telephone or virtual treatment sessions.

Has the use of ’telerehab’ been of benefit to you? 

Yes absolutely! It has enabled our teams to keep in touch with each other in a more personal way. I must admit to preferring to be able to see people rather than telephone conferencing. It feels a little bit more like a face-to face meeting. I definitely think the use of online technology has proved to be a real asset during the pandemic. Professionally I have used Zoom, Microsoft Teams and Air Meet. These platforms have been great for attending meetings and staying connected with colleagues. I’ve also had access to lunchtime yoga and mindfulness training delivered by Bush & Co and webinars kindly hosted by law firms.

How have your clients responded? Was it difficult for them to adapt to? 

Most of my clients have been open to communicating via telerehab. One of the issues we have encountered is that they are often using mobile phones or tablets and their devices have been unable to open the meeting links to Zoom. Generally, my client group have preferred to use the camera feature on social media apps, such as, WhatsApp or speak over the telephone.

Do you feel the lack of face-to-face contact with clients or/and colleagues has been damaging?

If face-to-face contact has been identified as needed by the risk assessment and it’s been clinically safe and appropriate to meet in person, I have continued to visit clients so this has avoided causing any damage. I must say I have certainly missed seeing my colleagues in person but don’t think it has been damaging because we have used the virtual resources. Bush & Co has introduced ‘Happy Post’ so we’ve been connecting through good old fashioned letterbox mail as well as electronic ‘Postcards from Home’ which have been a way to see how other people’s lives have changed during the pandemic.

How central do you think the use of telerehab will be for you going forward? 

I think telerehab will change our working practices and we will attend more virtual team meetings, multi-disciplinary team meetings, webinars and training sessions etc.  Moving forward I will definitely consider telerehab for my clients but I don’t think it is a replacement for face-to-face client visits because of the nature of our work. I think a blended work approach is definitely the way forward.

How do you think the future of case management has been shaped by the pandemic? 

I think there is a much better understanding of what home working is; the challenges, opportunities, limitations and rewards that it brings. Pre-pandemic I would use telephone or face to face client contact. The pandemic has made us aware of a third option – telerehab. It’s also opened up access to new providers of therapies and rehabilitation which would have normally been restricted due to distance from the client.

Will you be doing anything differently within your business going forward compared to pre-pandemic? 

I have learnt during the pandemic the importance of physical contact with my clients. This is something I have probably taken for granted throughout my career. Some clients need this more than others, for example, because of lack of IT skills or cognitive impairment. There are clients though that engage really well using telerehab so moving forward I will definitely be embracing a blending working approach. Ultimately the clients’ needs have always been at the heart of the decisions we make and so going forward we’ll be taking our learnings forward in terms of telerehab needs too. Our clients are often vulnerable and may be anxious or reluctant to get back to ‘normal’ so we won’t be rushing.

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