Healthy people with a higher genetic risk of Alzheimer’s disease may show differences in brain structure and in cognitive test scores relating to reasoning and attention, a new study has revealed.
The research suggests that, although the association between these differences in people with a higher genetic risk of Alzheimer’s disease were small, signs of the neurodegenerative disease may be detectable before significant symptoms are obvious.
The study, from the University of Glasgow, is the largest study to date investigating the genetic risk for late-onset Alzheimer’s disease and non-demented structural brain MRI and cognition phenotypes.
Its findings have been hailed as a potential “real game changer” by the Alzheimer’s Society.
Alzheimer’s disease (AD) affects several brain regions, but among the earliest includes the hippocampus, which is vital for processing memory and learning.
Genetic factors are known to play a role in developing AD dementia, and researchers can use polygenic risk scoring – a method used to estimate an individual’s genetic risk of developing a particular disease, such as AD.
In this study, the researchers calculated a polygenic genetic risk score based on a large number of mutations for 32,790 generally-healthy adults without dementia from the UK Biobank, a large-scale biomedical database and research resource, to see if their lifetime genetic risk of AD was associated with average differences in brain structure and cognitive performance.
Rachana Tank, a lead author on the study, said: “Our findings are novel because they show the effects of genetic risk may, to a certain extent, be apparent long before a clinical dementia diagnosis. Although we cannot say for certain that these differences are early signs of dementia per se, it is important that we do further research in this area.
Dr Donald Lyall, from the University’s Institute of Health and Wellbeing, said: “These findings could lead to a better, more meaningfully informative way of gauging Alzheimer’s disease risk than current methods of inquiring about a family history of dementia, as being able to identify individuals at risk of worse cognitive abilities and potentially accelerated decline could greatly improve diagnosis and treatment options in future.”
Fiona Carragher, director of research and influencing at Alzheimer’s Society, said: “If we can accurately identify people at risk of developing Alzheimer’s disease later in life, it could be a real gamechanger.
“Early detection of those at a higher risk has the potential to pave the way for new treatments in the future and help researchers understand what causes diseases like Alzheimer’s to develop.
“The scale of this study is significant. It adds further evidence to the theory that some brain changes associated with Alzheimer’s disease can start many years before symptoms such as memory loss.
“However, it only looked at people from a white European background – we need to better understand whether there are associations between different genetic risk factors and changes in the brain in people from other ethnic communities.
“Research will beat dementia, but we need more funding. The Government must honour their commitment to double dementia research funding to provide hope for future generations. We owe to the 850,000 people in the UK currently living with dementia.”
Support at your fingertips – new resources for family dementia carers
Dementia Carers Count (DCC) is a national charity offering free, life-changing, practical support for families living with dementia.
The charity has just launched its new Virtual Carers Centre and runs regular online learning sessions, enabling carers to access essential support wherever they are.
DCC gives family carers the opportunity to understand more about dementia, to connect with others in a similar situation and to look after themselves while navigating the highs and lows of caring for someone with dementia.
It’s the ideal place to signpost carers to, for information and resources to help them with their day to day challenges.
Here is Stuart’s story.
Stuart met Roger in 1985, they’ve been in a registered partnership since 1995. Roger was diagnosed with young-onset Alzheimer’s when he was 57.
Roger has deteriorated considerably since his diagnosis and, as well as caring for him full time, Stuart has had to take on more and more at home.
Although Roger’s interests have changed his mood has remained good. He’s always smiling, and people tend to be drawn to him.
Stuart feels a bit frustrated now that he’s increasingly having to do more and more for Roger. He didn’t choose to be a carer and thought that by now, he would be enjoying my retirement and living happily ever after.
At the start of the pandemic Stuart began using technology like Zoom. He first found out about Dementia Carers Count (DCC) in an online, young-onset support group. He registered for some of DCC’s online learning sessions.
“The online courses have been like gold dust and have increased my knowledge of dementia and Alzheimer’s. The people leading the sessions are easy-going, supportive and understanding…. They’ve been a lifeline for people like me during the pandemic.”
“DCC’s digital services are fantastic. They are very informative, accessible, and the content is presented in a way that is easy to understand. During the sessions, you can talk about your specific challenges and connect with the other people attending. “
Stuart says that the support DCC provides him has helped him immensely and is extremely useful to anyone in a caring situation.
“The information comes from people with experience and knowledge. It will help you understand what is going on for the person you care for and develop a better caring strategy. Everyone running the sessions is very patient and nurturing towards the people attending.”
DCC is here to help families living with dementia.
DCC’s Virtual Carers Centre is a brand new resource for family or friends who are looking after someone with dementia. It’s accessible any time; day or night, complete with articles, videos, presentations and more.
Carers will find all the support they need, including:
✔️ Practical information about carers’ rights and benefits
✔️How to manage everyday emotions and changes in behaviour
✔️Wellbeing strategies for carers and for the person they are supporting
✔️The opportunity to book on to Live Online Learning sessions covering various topics
T: 020 3096 7895 E: email@example.com
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De-cluttering ‘may not help’ with dementia
People with moderate dementia performed better when surrounded by their usual clutter, a new study has revealed
A clutter-free environment may not help people with dementia carry out daily tasks in the way that has traditionally been thought, a new study has revealed.
Researchers at the University of East Anglia (UEA) studied whether people with dementia were better able to carry out tasks, such as making a cup of tea, at home – surrounded by their usual clutter – or in a clutter-free environment.
And they admit to being “surprised” to find that participants with moderate dementia performed better when surrounded by their usual clutter.
But the different environments made no difference to people with mild and severe dementia, who were able to perform at the same level in both settings.
Professor Eneida Mioshi, from UEA’s School of Health Sciences, said: “The majority of people with dementia live in their own home and usually want to remain living at home for as long as possible.
“So it’s really important to know how people with dementia can be best supported at home – one possible route would be by adapting the physical environment to best suit their needs.
“As dementia progresses, people gradually lose their ability to carry out daily tasks due to changes in their cognitive, perceptual and physical abilities. Participation in daily tasks could then be improved by adapting the person’s environment.
“To this end, we wanted to investigate the role of clutter in activity participation, given the potential to use de-cluttering to support people with dementia to continue to be independent.
“Environmental clutter has been defined as the presence of an excessive number of objects on a surface or the presence of items that are not required for a task.
“It is generally assumed that a person with dementia will be better able to carry out daily tasks when their home space is tidy and clutter free.
“However, there has been very little research to really test this hypothesis.
“We wanted to see whether clutter was negatively affecting people with dementia. So we studied how people at different stages of dementia coped with carrying out daily tasks at home, surrounded by their usual clutter, compared to in a clutter-free setting – a specially designed home research lab.”
Occupational therapist and PhD student Julieta Camino carried out the study with 65 participants who were grouped into those with mild, moderate and severe dementia.
They were asked to carry out daily tasks including making a cup of tea and making a simple meal, both at their own home and at UEA’s specially-designed NEAT research bungalow – a fully furnished research facility that feels just like a domestic bungalow.
The researchers evaluated performance of activities in both settings, and also measured the amount of clutter in the participants’ homes. Meanwhile, the NEAT home setting was completely clutter free.
Julieta, also from UEA’s School of Health Sciences, said: “We thought that the complete absence of clutter in our research bungalow would play a beneficial role in helping people with dementia with daily living activities. But we were wrong.
“We were surprised to find that overall, people with moderate dementia, in particular, performed daily tasks better at home – even though their homes were significantly more cluttered than our research bungalow.
“And it didn’t seem to make any difference how cluttered the participant’s home was. The only factor that contributed to how well they could carry out tasks at home was their level of cognition – with those with severe dementia encountering the same difficulties to perform the tasks at home and in the research bungalow.”
This research received funding from the Alzheimer’s Society and National Institute of Health Research (NIHR) Applied Research Collaboration East of England (ARC EoE) programme.
New drug design could yield Alzheimer’s treatments
The breakthrough could have the potential to create superior new drugs to improve cognitive function in Alzheimer’s disease patients
A breakthrough ‘bench to bedside’ discovery, ten years in the making, has been made in the quest to advance the future treatment of Alzheimer’s disease in patients.
The research illustrates – for the first time – the process of designing a new molecule to selectively target a specific receptor protein in the brain and demonstrating, through laboratory preclinical and human clinical studies.
The breakthrough has been hailed as having the potential to create superior new drugs to improve cognitive function in Alzheimer’s Disease patients.
The study – conducted at the University of Glasgow with Sosei-Heptares Ltd – was focused on new molecules, designed by the biotechnology company, that selectively target a protein called the M1 muscarinic acetylcholine receptor (or M1 receptor, a G protein-coupled receptor or GPCR) in the brain, which is known to play a central role in memory and cognition.
Subsequent translational medicine studies tested the hypothesis that such molecules will retain cognitive benefits and lack dose-limiting side effects.
The international research team demonstrated that an exquisitely selective modulator could be successfully designed using detailed knowledge of the M1 receptor’s 3D structure, despite its very close similarity to other types of muscarinic receptor. This approach is known as structure-based drug design or SBDD.
Subsequent pre-clinical studies confirmed the designed molecule retained optimal properties for improving memory while minimising side effects associated with previous attempts to target the M1 receptor.
Finally, clinical studies demonstrated that the M1-selective clinical candidate HTL9936, at meaningful doses in healthy volunteers, showed greatly reduced side effects relative to many non-selective predecessors from programmes spanning a generation of traditional drug discovery approaches.
These ground-breaking results substantiate the hypothesis and the power of novel approaches using 3D structures of receptors developed by the team can be applied to the M1 receptor to create a potential new medicine for Alzheimer’s Disease patients, and also have broader implications highlighting a new approach to address other GPCRs linked to a wide range of diseases.
Prof. Andrew Tobin, professor of molecular pharmacology and director of the newly-built Advanced Research Centre at the University of Glasgow, said: “This is a true bench-to-bedside discovery, many years in the making, and we are thrilled that this hugely important and global collaboration with our partners at Sosei Heptares and others has resulted in a highly sophisticated drug design approach that offers huge potential to improve the treatment of Alzheimer’s Disease, by activating memory and cognitive centres within the brain.
“We are extremely encouraged by our findings so far and are very hopeful that this could lead to new treatment options for patients with this devastating disease.”
Dr Miles Congreve, chief scientific officer at Sosei Heptares, added: “We are delighted that this pioneering drug design work in collaboration with Prof. Tobin and others has been published in such a highly acclaimed journal.
“The precision SBDD technology that we have developed is core to our approach at Sosei Heptares and has been extremely effective for designing new and superior drug molecules that we are progressing through preclinical and clinical development as potential new treatments for a wide range of neurological, immunological and gastrointestinal diseases.”
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