Summer Research…APOE in mid-adulthood

Recently I was given the opportunity to do research with the Rusted Lab at Sussex University as a Junior Research Associate. This means I will be continuing the Rusted Lab’s current work measuring the effects of the APOE e4 gene on cognition in mid-aged adults and, hopefully, be able to further our understanding of how and when this gene begins to show detrimental effects on cognition in carriers.

Now for a brief introduction to myself; I am an undergraduate student at Sussex University studying Neuroscience with a pathway in Psychology. I applied, and was (thankfully) accepted, for JRA funding to do research in Jenny’s lab over the summer and have been doing so for 3 weeks now. Since starting my degree in Neuroscience, I have found that the cognitive and behavioural aspects of the science are what I find most interesting, especially in the broad field of memory research. When searching for JRA opportunities, the work being done in the Rusted lab stood out to me; not just because of its contemporary prominence or focus on the genetic basis of cognition (a topic I find very interesting), but also because of the very obvious real world relevance of the research.

My project will aim to develop a collaborative study between the Rusted Lab at Sussex University and Prof. Graham’s Lab at Cardiff University, to establish a clear cognitive profile in mid-age e4 carriers, and to map these against structural brain changes in a group of mid-age volunteers. Significantly, I will test the Rusted cohort of mid-age volunteers on tasks from each lab (a Prospective Memory (PM) task and Visual Paired-Comparison (VPC) task). Secondly, with advanced image analysis support from the CUBRIC facility in Cardiff, I will cross reference cognitive effects against the archived structural imaging data for this group. This will hopefully add to our understanding of age related cognitive changes in e4 carriers as well as differences in mid-age e4 and e3 (the population norm) carriers.

As it’s early days, I don’t yet have any earth-shattering results to share, but I am very excited to see what is possible in APOE research and to continue learning a lot about the correlation of this gene and Alzheimer’s-type dementia.

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Orla Bonnar: Visit to memory clinic 29 March 2017

As part of my Alzheimer’s Society funded PhD, I was afforded the opportunity to attend a multidisciplinary team (MDT) meeting held by the memory assessment service (MAS) team in Brighton.  The aim of this service is to ‘provide early detection, diagnosis, treatment and care if you have problems associated with dementia’.

The meeting was attended by various members of the team, each with their own unique contribution to patient care.

The first person I met was a memory support worker who explained her role and valuable contribution to the care of local dementia patients. She explained how she visits people with dementia in their own home to assess their needs and provide the support that they require. Her contribution to the meeting allowed the team to make rounded and individualised decisions regarding each patient’s care.

Also present were two specialist general practitioners, a consultant psychiatrist and two specialist nurses. Together they made their way through a long list of local patients who had recently experienced memory problems and had been assessed using various tests such as the MMSE (mini mental state examination). They used each patient’s performance on these tests, combined with their medical history, to diagnose which type of dementia each patient had and which, if any, treatment was most suitable. The team would then make a personalised plan to ensure each patient received appropriate follow up care.

One of the most striking things I noticed was how few of the patients were eligible for pharmacological treatment, further highlighting the need for an increased number of treatment options that are more effective and are suitable for a wider population of patients. As well as this it is incredibly difficult to diagnose patients with the correct type of dementia, emphasising the importance of these skilled and dedicated professionals.

This visit helped to highlight some of the work that is being done to support those experiencing memory problems in the local community. It also made it clear to me that, although I am familiar with biological aspects of the disease, there is a lot to learn about the impact of the condition on the lives of those who are affected as well as those who care for them.

Orla Bonnar is a PhD student working with Dr Catherine Hall,  and funded by the Alzheimer Society as part of the APOE AS DTC at Sussex

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Alzheimer’s Society funding announced…

Yesterday the Alzheimer’s Society announced another major investment in research to improve quality of life and the quality of support available to people affected by dementia, funding three new research programmes with £2m each over the next five years. Professor Rusted is co-investigator on one of these projects, a collaboration between  Professor Linda Clare at Exeter University and the universities of SussexCardiffBrunelBangor and Newcastle with King’s College London, the London School of Economics, the RICE centre in Bath and Innovations in Dementia CIC, focusing on ways to measure and improve quality of life for people affected by dementia. The grant will fund a second phase of the group’s large-scale national study entitled Improving the Experience of Dementia and Enhancing an Active Life (IDEAL), which, since 2014, has been gathering an extensive database of information from over 1500 people with dementia and 1300 carers, using questionnaires and interviews to understand the experiences of people with dementia as they move through from diagnosis to the later stages.  The expansion of the study allows us to follow this large and diverse cohort over six years of progression, including the less-researched experiences of people from black and minority ethnic backgrounds and people in the advanced stages of dementia. At the end of the study we will use our findings to set out guidelines for how to help people affected by dementia to have the best possible quality of life.

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Dementia Action Alliance Launch Event

DAA photo.jpg

(from left to right) Professor Louise Serpell (Joint AS DTC lead, Life Sciences), Rachel Clarke (PhD student: Psychology, Social Policy), Rebecca Atkinson (PhD student: Alzheimer’s Society Doctoral Training Centre), Dr Karen Marshall (Research Fellow, Life Sciences).

We recently attended the launch event of the Brighton chapter of the Dementia Action Alliance. The Dementia Action Alliance brings together people working on or with dementia, people living with dementia, and those that care for people living with dementia. Their actions facilitate information sharing, and aim to improve the lives of people affected by dementia.

The event featured many interesting talks, helping to raise awareness of local work to improve the quality of life for people living with dementia, and allowed us to discuss some of the research activities ongoing at the University of Sussex with a network of interested individuals. It was great to mingle with many different people working on or with dementia; researchers, charities, businesses offering support services, and of course individuals directly affected by dementia, their families, and carers.

Among the many interesting talks, there was a Dementia Friends training and awareness session. Dementia Friends is a wonderful program run by the Alzheimer’s Society, aiming to change people’s perceptions of dementia. We were so impressed by the training that Professor Serpell arranged for a Dementia Friends session to be held at the University of Sussex, for staff and students.

The key objectives set out by Brighton and Hove Dementia Action Alliance are:

  1. To work in partnership together with businesses, the local authority, the voluntary sector and most importantly with people living with dementia so Brighton and Hove achieves recognition as a Dementia Friendly Community. The DAA coordinator will support and encourage organisations to submit action plans to demonstrate how they will become more dementia friendly.
  2. Through specific local named providers (The Trust for Developing Communities; Engage and Create; local Dementia Champions), to ensure that  Dementia Awareness is raised significantly within Brighton and Hove.
  3. By setting up new local forums, for example with Brighton Carers Centre, and others to ensure sustainability is built into the local DAA service model. Links will also be made with local Dementia Cafés, the Age Friendly City forum and other dementia friendly community groups
  4. Be committed to  increasing the  health and wellbeing of people with dementia and their carers in Brighton and Hove by looking at local physical activity programmes, for example dementia friendly gardening.
  5. To address and reduce social isolation of people with dementia and their carers
  6. To ensure that people with dementia and their carers experience significant improvements in their experience of living in Brighton and Hove

 

More information on the Brighton and Hove Dementia Action Alliance can be found here. 

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Disrupted neural activity patterns to novelty and effort in young adult APOE-e4 carriers performing a subsequent memory task

Introduction

The APOE e4 allele has been linked to poorer cognitive aging and enhanced dementia risk. Previous imaging studies have used subsequent memory paradigms to probe hippocampal function in e4 carriers across the age range, and evidence suggests a pattern of hippocampal overactivation in young adult e4 carriers.

Methods

In this study, we employed a word-based subsequent memory task under fMRI; pupillometry data were also acquired as an index of cognitive effort. Participants (26 non-e4 carriers and 28 e4 carriers) performed an incidental encoding task (presented as word categorization), followed by a surprise old/new recognition task after a 40 minute delay.

Results

In e4 carriers only, subsequently remembered words were linked to increased hippocampal activity. Across all participants, increased pupil diameter differentiated subsequently remembered from forgotten words, and neural activity covaried with pupil diameter in cuneus and precuneus. These effects were weaker in e4 carriers, and e4 carriers did not show greater pupil diameter to remembered words. In the recognition phase, genotype status also modulated hippocampal activity: here, however, e4 carriers failed to show the conventional pattern of greater hippocampal activity to novel words.

Conclusions

Overall, neural activity changes were unstable in e4 carriers, failed to respond to novelty, and did not link strongly to cognitive effort, as indexed by pupil diameter. This provides further evidence of abnormal hippocampal recruitment in young adult e4 carriers, manifesting as both up and downregulation of neural activity, in the absence of behavioral performance differences.

 

Evans, S.Dowell, N. G.Tabet, N.King, S. L.Hutton, S. B. and Rusted, J. M. (2016), Disrupted neural activity patterns to novelty and effort in young adult APOE-e4 carriers performing a subsequent memory taskBrain and Behavior00111. e00612, doi: 10.1002/brb3.612

For full access to the paper click here

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Doing a PhD in the Alzheimer’s Society Doctoral Training Centre at Sussex –being part of a team and enjoying it!

DTC-74

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The Elusive Nature of APOE ε4 in Mid-adulthood: Understanding the Cognitive Profile

Objectives: The apolipoprotein E (APOE) ε4 allele is an established risk factor for dementia, yet this genetic variant is associated with a mixed cognitive profile across the lifespan. This study undertakes both a systematic and meta-analytic review of research investigating APOE-related differences in cognition in mid-adulthood, when detrimental effects of the allele may first be detectable.

Methods: Thirty-six papers investigating the behavioral effects of APOE ε4 in mid-adulthood (defined as a mean sample age between 35 and 60 years) were reviewed. In addition, the effect of carrying an ε4 allele on individual cognitive domains was assessed in separate meta-analyses.

Results: The average effect size of APOE ε4 status was non-significant across cognitive domains. Further consideration of genotype effects indicates preclinical effects of APOE ε4 may be observable in memory and executive functioning.

Conclusions: The cognitive profile of APOE ε4 carriers at mid-age remains elusive. Although there is support for comparable performance by ε4 and non-e4 carriers in the 5th decade, studies administering sensitive cognitive paradigms indicate a more nuanced profile of cognitive differences. Methodological issues in this field preclude strong conclusions, which future research must address, as well as considering the influence of further vulnerability factors on genotype effects.

Lancaster, C., Tabet, N., & Rusted, J. (2016). The Elusive Nature of APOE ε4 in Mid-adulthood: Understanding the Cognitive Profile. Journal of the International Neuropsychological Society, 1-15.

For full online access to the article click here

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5 Tips from a Thesis Writing Boot Camp

Right before the holiday season, I decided to attend the Sussex University Doctoral School’s Thesis Boot Camp and was pleasantly surprised by how much I accomplished and learned. One limitation was that the writing workshops mostly catered to the humanities so, in addition to sharing top tips, I’ll also be translating the strategies (on the fly) for us psych folk. I’ll also note how the strategies differ from (incorrect) implicit assumptions I’ve held:
  1. Develop a routine that works for you, specifically: I’ve held onto the implicit assumption that there is a “right” way to do a PhD despite my supervisors and classmates telling me no. Despite this, I know there are others like me comparing themselves to other doctoral students and subsequently, feeling inferior. At thesis boot camp, we were encouraged to figure out what works for us
  2. Try and remove any psychological barriers between you and your writing: …No one at boot camp actually said that, but I think it summarizes what Liz was trying to get across. Specifically: writing is a form of thinking. It’s difficult to form an argument until you start writing so “shut up and write!” That being said, the reason we were told previous attendees wrote as many as 20,000 words in one weekend was because it was “first draft material” or what I refer to as my “messy outline.” As we all know,  psychology articles tend to be pretty information-dense; thus, I knew that if I was going to get anything out of this intensive writing weekend, I needed to bring along some version of my messy outline and then write from that. I also spent half a day editing what I’d already written. Thus, I “only” managed to write 6,000ish words, but I still felt pretty proud of myself (for the most part).
  3. On the subject of editing, dont edit while you write: Something I found REALLY helpful was the notion that multi-taking while writing is not time- or cognitively-efficient. This idea might seem like common sense, but if you’re anything like me, you rarely listen to logic when it comes to writing well, because writing a thesis is stress-inducing. Well, because the boot camp was only two days, I thought I might as well give this logical notion a whirl and by George, it worked! When I was writing content, I only let myself make tiny edits on the sentence I’d just written (because that’s how I write), and I’d try not to let myself go back and read what I just wrote (my worst, self-induced time-suck). After that, I’d only let myself do organization, content-based edits (we were encouraged to break down the process of editing into distinguishable tasks), etc and then, when I was happy with what I was trying to say, I’d copyedit.
  4. Collect evidence based on facts, not emotions: we were encouraged to try out the pomodoro technique (25 mins on, 5 mins break x 3, 25 mins on, long break – REPEAT) for the morning of the first break. Liz encouraged us to base our daily/weekly goals on how much work you achieve on average during one pomodoro in addition to how many pomodoros you can realistically do in a day. I know that at least for me, if I’m feeling particularly motivated, I’ll set myself a word-count goal that is way to high. The only issue with this is that I end up disappointing myself rather feeling accomplished by the end of the day.
  5. If your time management/organization method stresses you out, find/make a new one: If you’re anything like me, getting through your doctorate is a mind-warp (in lieu of a different phrase). Not only is the work challenging, but, because we’re often not credited for how difficult it is to go from dependent undergrad (or whatever) to independent, kickass researcher, we end up feeling inferior to our classmates. I think this is a mind-game that more PhD students would benefit from tackling. There is no right way to do a PhD and thus, there is no right way to organize your time! 
I have more notes from what I learned at Thesis Boot Camp but not enough time to write all of them up (this girl has got to finish her thesis). That being said, if you’re keen to hear more of my ramblings, I’d love to go for a coffee. If you know me, you know I’m pretty chatty. My email is m.berenhaus@gmail.com.
Molly Berenhaus
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Dementia in the clinic

One of my PhD colleagues, Rebecca Atkinson, wrote recently that each student at Sussex funded by the Alzheimer’s Society charity is afforded the opportunity to complete placements in a local Memory Assessment Services (MAS) clinic. I was paired with Consultant Psychiatrist Dr Cathy Ulliott, who specialises in old age psychiatry, and have attended the outpatient centre in Shoreham twice since May.

On my first visit, I met with Cathy to discuss the process that patients in this area of Sussex experience when they are referred to the MAS team. In different NHS regions, the practice can differ, but in the local Sussex area, patients will be referred by their GP to the MAS team, and first contact is typically with a specialist nurse, with whom the patient will complete a number of assessments including the ACE (Addenbrookes Cognitive Examination). The patient will typically also have a brain scan. Together, assessments such as these help the clinician build a picture of a person’s performance in cognitive domains of language, spatial ability, problem solving, and aspects of memory, alongside being able to determine whether any damage, degeneration, or reduced vascular supply is evident in the brain.

On my second visit, I attended Dr Ulliott’s clinic, in which she met with three patients. The primary role of these appointments was to establish a diagnosis for each individual, based upon the results of the assessments, in combination with information on the individual’s family and medical histories, and interviews with the patient and their carer(s) in terms of how their cognitive difficulties might be presenting in their everyday life. Following diagnoses and administration of treatment (where possible and appropriate), patients would meet with the Dementia Advisor on-site, who is employed by the Alzheimer’s Society. The Dementia Advisor is able to help the patient and their carer navigate Social Services’ Care Needs Assessments, give information on the different types of dementia, and provide materials and contacts for social and professional support available in the local area.

The patients I observed were aged between 78-82, two male and one female; all three patients were given diagnoses of mixed dementia, vascular dementia with Alzheimer’s. What struck me most keenly during my observation of the sessions however, was the difference between each of these patients’ abilities despite receiving the same diagnosis, and being of similar ages. Differences were noticeable in terms of the patients’ capacity to recognise and articulate their abilities and limitations, and the reports from the caregivers accompanying the patient (in all three cases, the patient’s spouse), but most surprising to me was the differences that were evident in each individual’s ability to perform in the memory assessment tests, and the extent their problems affected their completion of everyday tasks and ability to live a full life.

The differences between each of the patients I saw in Dr Ulliott’s clinic brought home to me the extent to which other aspects of health can affect the subjective patient experience of having dementia, as well as the way in which individual differences and life experiences may affect both the personal experience and observable development of dementia/cognitive decline at certain stages – an aspect particularly relevant to research being conducted at Sussex.

I was also struck by how difficult it can be to establish accurate diagnoses of the various forms of dementia, and the importance of the expertise and discernment of the Psychiatrist in their analysis not only of the clinical test results, but of the conversations, reporting of symptoms and lifestyle effects of the memory and cognitive problems obtained from the patient and their carer. I found the visit to the MAS clinic extremely informative and look forward to visiting with Dr Ulliott again.

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The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Possession of an APOE e4 allele is an established risk factor for Alzheimer’s disease, while the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. 66 volunteers, aged 45-55 years, completed three tasks that provided complementary measures of attentional control: prospective memory, sustained attention and inhibition. Performance was compared between e2 carriers, e4 carriers and e3 homozygotes (the population norm). Carriers of the e4 allele showed subtle disadvantages, compared to the e3 group, in accuracy of Stroop task and prospective memory performance. Contrary to expectations, e2 carriers showed performance disadvantages in sustained attention. The finding of detrimental effects in attentional control for both e4 and e2 complicates the current model that proposes opposing effects of these variants on later-life cognition. Future research is needed to understand how cognitive differences develop with increasing age, and the physiological mechanisms that underpin these changes.

For full online-access to the article click here

Title
The APOE paradox: how do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline
Published in
Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2016.08.015
Authors

Claire Lancaster, Naji Tabet, Jennifer Rusted

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