Researchers remain perplexed as to what causes dementia and how to treat and reverse the cognitive decline seen in patients.
In a first-of-its-kind study, however, researchers have discovered that cis P-tau, a toxic, non-degradable version of a healthy brain protein, is an early marker of vascular dementia (VaD) and Alzheimer’s disease (AD).
Their results define the molecular mechanism that causes an accumulation of this toxic protein.
Furthermore, they showed that a monoclonal antibody (mAb) that targets this toxic protein was able to prevent disease pathology and memory loss in AD- and VaD-like preclinical models.
Additionally, this treatment was even capable of reversing cognitive impairment in an AD-like preclinical model.
The study was conducted by researchers at the Medical University of South Carolina (MUSC) and Beth Israel Deaconess Medical Center (BIDMC) at Harvard Medical School.
Onder Albayram, co-lead author and assistant professor in the Division of Cardiology in the Department of Medicine at MUSC, said: “We believe our findings have not only discovered cis P-tau as a previously unrecognized major early driver of VaD and AD but also identified a highly effective and specific immunotherapy to target this common disease driver for treating and preventing AD and VaD at early stages.”
Aging is a normal part of life – we experience weakening of our bones and muscles, stiffening of our blood vessels and some memory lapses.
But for around 50 million people worldwide, these memory lapses become progressively more severe, ultimately leading to a diagnosis of dementia.
Dementia is an umbrella term that covers AD, which accounts for 60 to 80 per cent of cases; VaD, the second most common cause; and other less common pathologies.
Currently, there are no effective treatments for AD. Interestingly, most AD cases have a vascular component, suggesting a broader relationship between cognitive function and healthy brain vasculature.
A better understanding of that relationship could provide a platform to discover novel therapeutic targets.
“Our work provides evidence that cis P-tau may be a pathogenic factor that explains VaD, which is not generally linked to other dementias,” added Chenxi Qiu, co-lead author and a postdoctoral research fellow at BIDMC, Harvard Medical School.
In a preclinical model of VaD, young mice showed signs of brain inflammation and memory loss within one month.
However, treating these mice with the cis P-tau mAb prevented neural degradation and cognitive decline out to six months. In a separate preclinical model of AD, old mice showed severe cognitive impairment.
This severe impairment was significantly reversed when mice were given the cis P-tau mAb.
“These data show that cis P-tau could be an early upstream pathogenic factor common to both diseases,” said Albayram.
Translating information gained from preclinical models to humans is often difficult, but this study offers reasons to be optimistic.
Accumulation of cis P-tau caused dramatic changes in the genetic architecture of affected cells in a VaD model; these changes were consistent with those seen in human AD patients.
The researchers went on to show that treatment with the cis P-tau mAb reversed 85 to 90 per cent of those changes suggesting the power of this potential therapy.
“The genomic landscape really adapts after the silencing of this toxic protein,” said Albayram. “That was a big discovery.”
Not only are Albayram and Qiu excited about these findings, but colleagues at MUSC are already quite enthusiastic about this work.
The research opens the door for new potential immunotherapies and highlighted several new areas of research that need to be explored.
While the researchers delineated a pathway that leads to the accumulation of cis P-tau, the underlying linkage between vascular abnormalities and activation of the pathway needs to be identified.
A better understanding of how toxic cis P-tau interacts with the healthy trans P-tau could provide further insights into the progression of AD disease.
AD and VaD might not be the only diseases affected by high levels of cis P-tau. Other brain disorders with a vascular component might also arise from this toxic protein, but further study will be required to establish such a link.
“Cis P-tau may be a common, early and pathogenic factor underlying traumatic brain injury, VaD and AD,” said Qiu.
As we get older and our memory begins to lapse – misplacing our car keys or forgetting the name of a new acquaintance – we fear the possibility that these are the first signs of dementia.
And while there is currently no approved treatment to reverse the physiological effects of dementia, this new research may provide hope that new therapies are around the corner.
Alzheimer’s Research UK receives diagnostics funding boost
Alzheimer’s Research UK to receive up to US$2m in funding to produce a digital toolkit of apps and wearable technology aimed at aiding earlier diagnosis.
The US Alzheimer’s Drug Discovery Foundation (ADDF) has announced up to US$2m of funding for a collaborative research initiative led by Alzheimer’s Research UK to develop a digital toolkit of apps and wearables to detect the earliest stage of Alzheimer’s.
The funding awarded to the Early Detection of Neurodegenerative Diseases (EDoN) initiative is part of the ADDF Diagnostics Accelerator (DxA), which challenges the global research community to innovate new diagnostic technologies for dementia and Alzheimer’s.
Early detection of neurodegenerative diseases
EDoN is a project led by Alzheimer’s Research UK which combines global experts in data science, digital technology and neurodegeneration. It monitors sleep, fine motor control, heart rate, speech and brain activity to develop digital signs of early disease that could improve dementia research efforts in the future.
EDoN aims to streamline efforts to collect, integrate and analyse a wealth of digital, clinical and health data to help identify the disease earlier.
The data can be compiled to build machine learning models to identify patterns of early disease-specific to different neurodegenerative diseases.
The project aims to incorporate the best measures into an inexpensive and easy-to-use digital toolkit. This will likely be a combination of apps, wearable or mobile devices and software.
Funding and research
The funding will allow the team of researchers to collect digital data from over 600 people who are currently involved in two population-based cohort studies in Australia.
The participants are asked to wear a headband to measure sleep and brain activity, an activity tracker to register heart rate and physical activity.
This will be combined with a smartphone app that measures cognitive function such as speech or fine motor control. This data will be compared to clinical data from the cohorts to help researchers identify the digital measures linked to biological changes.
Participants in the study include people with different levels of Alzheimer’s disease, those with mild cognitive impairment and cognitively healthy volunteers. This will allow researchers to view a wide range of responses across a spectrum of cognitive health. They will follow the individuals involved over time identifying any changes that occur.
The diagnostics Accelerator provides funding to increase the development of affordable and accessible diagnostic tools and biomarkers for the disease. The initiative currently funds over 30 projects around the world including a number of blood tests and eye scanning techniques. These tests monitor the early biological changes due to Alzheimer’s disease.
These changes may be undetectable to the human eye but may be picked up by digital technologies.
Dr Zoe Kourtzi, scientific director and chair of EDoN Steering Committee, said: “Around the world, there are 50 million people living with dementia — a number that is only set to rise. Global efforts to tackle the diseases that cause dementia are currently hamstrung by our inability to detect them early enough. Digital technology holds enormous potential to put us on the front foot when it comes to identifying diseases like Alzheimer’s earlier, and EDoN is working to make that happen.
“Accurate and cost-effective tools for detecting early neurodegenerative disease will provide essential insight into fundamental disease mechanisms, improve clinical diagnosis and enable existing and future interventions to be given earlier when they have the best possible chance of success.
“We are very excited to be working with the ADDF through the Diagnostics Accelerator. The funding will allow us to identify which digital measures have the most potential for early detection. The richer the data we can collect, and the more precise the algorithms we can develop, the faster we can move towards a digital toolkit that we hope will ultimately help doctors detect diseases like Alzheimer’s 10-15 years earlier than we can today.”
Seven devices that are revolutionising dementia care
Technology in the care system has come a long way, with the COVID-19 pandemic highlighting the need for more remote assistive technology.
A 2020 study from the University of Oxford found that 100 per cent of carers involved said they or their patients benefited from assistive technology.
With this in mind, NR Times takes a closer look at seven devices which are enabling greater independence and life quality for people with dementia.
SmartSole GPS tracker
One concern for families when their relatives with dementia live on their own is the fear that they will leave the house and get lost.
Research suggests this is quite a common problem, with an estimated 40,000 dementia patients going missing for the first time each year.
This is where the SmartSole GPS tracker can come in.
The product uses cellular technology to send its location every five minutes so relatives and carers can locate those living with dementia.
What makes the SmartSole unique is its discreteness. It fits into almost every shoe, so if someone does go missing, those with access to the monitoring system will be alerted straight away.
The Simple Music Player
Music can have a profound effect on people with neurological conditions. Being able to use the technology that provides this, however, can be difficult for those with dementia.
The Simple Music Player is a recommended product from the Alzheimer’s society and it makes listening to music straightforward.
Styled like a traditional radio – which is instantly recognisable for the elderly – the device is easy to use. Simply lift the lid and music will begin to play.
Also keeping things simple is the DayClox which makes timekeeping easy and understandable for dementia patients.
Available in both traditional and digital forms, the clock simply shows what day it is and whether it is morning, afternoon, evening or night.
Working out specific times can be a challenge for those with dementia, so the DayClox can assist when it comes to things like keeping track of when someone needs to take their medication.
Although not specifically designed for dementia patients, CaringBridge is a free platform that allows everyone involved in caring for an individual to keep up-to-date with their progress.
It gives carers the chance to set up a personal webpage for a patient, which they can post photo and video updates about how they are progressing.
Other people can visit the page, where they can like (called Well Wishes) and comment on the updates, as well as reading their personal story and journal updates.
The Extra Simple Dementia Mobile Phone – Doro 580
The Extra Simple Dementia Mobile Phone, by tech giants Doro, takes away any complication around giving a loved one a phone call.
If the last year has taught us anything, it’s the importance of keeping in touch with loved ones; and some studies suggest that loneliness can speed up the onset of dementia.
With its easy-to-use set up and large buttons, the Dementia Mobile Phone makes calls seamless. Simply link a phone number to each button and press to begin.
Looking for an all-in-one monitoring system? The Canary Care portal is a discrete, wifi-free system that tracks a person’s behaviour without the use of cameras or microphones.
Not only can it follow a person’s movements, bathroom visits and sleeping patterns, it also allows caregivers to track their home’s temperature, sending alerts if anything looks unusual.
Care can be shared around the family through the portal and reminders can be set to check that the proper medication is being taken.
Howz is similar to Canary Care as it allows those in charge of care to keep track of a person’s activity, notifying them if anything unexpected occurs.
Funded by NHSX, the system is unique as it can connect to a Smart Meter to monitor the electricity output in a person’s home.
This means it can detect any sustained electrical activity, which can help dementia patients in the event they forget to turn off their appliances.
Student creates innovative memory box to help dementia patients
Our senses can help trigger certain memories which are vital to keeping those with dementia connected, with one student from Edinburgh creating a tool to do just that.
A student from the Edinburgh Napier University has created a reminiscence therapy tool kit which is designed to help dementia patients recall past memories.
The Forget Me Not Box contains a number of tools that are used to activate the five senses, bringing joy to those with dementia while also helping retain their identity.
The kit is fully customisable so patients can explore memories and senses that are unique to them.
Its lid allows photographs to be displayed while the built-in speaker can play a patient’s favourite songs as well as voice notes from family and friends.
The box’s taste cards come with photographs and descriptions of a person’s favourite foods, while the scent bottles allow them to recall familiar smells such as similar perfumes.
All of this keeps a dementia patient’s identity, something which can often be lost particularly in a care home setting.
Furthermore it can be used to improve communication between family members, acting as a conversation starter when people come to visit.
Christy Orr is in the final year of her graphic design degree and created the box as part of her major project after her family’s past experiences with the disease.
“My grandma passed away from Alzheimer’s when I was younger so that’s kind of what motivated me to do the project,” Christy told NR Times. “She was diagnosed when I was quite young, but I do remember the whole diagnosis process.
“That was one of my earliest memories of her. I was there throughout all her dealings with Alzheimer’s until she passed away.”
“The box is mostly about identity and the fact that you still are that person even when you are diagnosed with dementia.”
Christy completed her dissertation around the causes of dementia worry and one of her main findings was this loss of identity among these patients.
This is what the Forget Me Not Box is aiming to do and has already shown its impact, having been tested on people at various stages of dementia.
“I’ve got the business limited at the moment,” Christy said. “I just need to sit down and think about how the box will actually be made, because currently it’s being made as a prototype out of the things that I had available at the time.
“It’s been sent out for testing and I’ve had some user feedback so far. I was sent some photos from a woman whose mum has dementia and she is in a care home.
“She gave her the box and put her own music in the sound module and some scents in the smell bottles, but she was most interested in the taste cards I created.
“It’s got different food and drinks or anything that you can taste on them, with a little description so it’s usually interesting reading them for those with dementia.”
Christy has also had a lot of help from Edinburgh Napier University, who think the box is a great idea.
“The university has been really supportive,” she said. “I haven’t actually received feedback or got my grade for my major projects yet but it’s been really good so far.
“They created a video about the box and posted it on social media to get the word out about it and they’re excited that I want to continue it on as well, more than just a project.
“I do want to get it to market because I think it’s a thing that could really help people.”
Although the Forget Me Not Box is still in the trial stages Christy wants to start distributing it as soon as possible to show its power.
Not only is the device helping those with dementia but it is also educating others around what it is to live with the condition, showing people that it is possible to live happy with a diagnosis.
“I think the box itself raises awareness that you don’t lose yourself to dementia and that you can still talk to that person that you know with the condition.
“Whether it be you grandma, a family member or a friend they are still the person that they are and the box enforces that.”
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