The Disconnected Mind aims to understand

how changes in the brain’s white matter – its connectivity – contribute to age-related cognitive decline in humans.

Newsletter 26: June 2014 Welcome to the Disconnected Mind summer newsletter. As ever, the last 3 months of 2014 have been highly productive for the study. This issue includes news and reports from events the team have been participating in over the last 3 months, plus the regular contribution from our colleagues at Age UK, as well as updates on study progress. Wave 3 of testing was completed at the end of last year and we are looking forward to starting Wave 4 of the study this summer/autumn. For more information about anything in the newsletter, get in touch particularly if you have something you would like to be included in a future issue. Contact details are on the last page. STOP PRESS! LBC Studies Featured on BBC Radio 4 Frontiers Programme Recently, BBC radio sent makers of the Frontiers show to interview LBC participants and Prof Deary about DMind research. The resultant programme - which also includes a controversial view on cognitive ageing – was broadcast on 11-06-14 at 9pm. If you didn’t hear it, you can listen again by following this link: http://www.bbc.co.uk/programmes/b0460kcl

LBC Reunion Event – April 17th 2014 A very special event this year was the reunion held at the General Assembly Hall in April to celebrate the completion of 3 waves of testing for the LBC1936, and 5 waves of testing for our sister study – the Lothian Birth Cohort 1921. The study team were delighted to welcome almost 400 participants on the day and those attending were able to speak to members of the research team that they had previously seen at the clinic, and also to some of the wider research team who analyse the collected data. Participants had the opportunity to ask them about their particular research interests, and to see their latest results in the posters that were on display. The afternoon began with talks from the principal investigators. Professor Ian Deary started the event with a reminder about the background to the study, its aims, and a summary of testing progress to date. In total, 697 participants from the LBC1936 were seen at the clinic for a third time, 488 had a second brain scan, and 173 consented to the LBC1936 Brain Tissue Bank. Ian also spoke about the success the research team has had with data from the LBC1936 and LBC1921 studies; 250 peer-reviewed scientific journal articles have been published to date, 23 of which have been published since January 2014 alone!

The Lothian Birth Cohorts’ Reunion at the General Assembly Hall, Edinburgh.

There was also an exclusive preview of the latest findings on bilingualism in the LBC1936 cohort, and the effects of smoking on the brain’s grey matter. Ian also presented data from the latest wave of assessments which showed that while – on average – there has been a slight decline on some mental tests (such as completing patterns or sorting letters and numbers), on others (e.g. vocabulary and memory for stories) there has been almost no decline at all. Up next was Professor Joanna Wardlaw, who leads the brain imaging aspects of the study. Joanna explained to the cohort members that MRI brain scans help us to investigate changes to the structure of the brain and how well its different parts are connected by the white matter. She also talked about how ultrasound images of the arteries in the neck can help to assess the impact of changes in blood flow to the brain. Two of the many key findings resulting from the LBC 1936 brain scans were then discussed. Smoking, high blood pressure and genetic influences can increase damage to the white matter, but exercise may help stop damage, and better initial white matter quality may be protective. To wrap up the first set of talks Professor John Starr gave an overview of how the cohort members are all doing in terms of their general health. Height and weight have shown very little change over the three visits to the clinic, with only ½ an inch decrease in height and 1lb loss of weight. Meanwhile, there has been a slight decline in fitness and strength, and an increase in illness. This is reflected in reports of activities of daily living becoming a bit more difficult. John concluded by highlighting the fact that the data from the LBC1936 study can help us to investigate the reasons for these changes.

Before stopping for a cup of tea, The Living Brain by filmmaker Anne Milne was premiered. This short film tells the story of our unique studies which look at the ways the cognitive ability of the brain changes as we grow older, and it reflects on the lives of those who take part in them. Anne’s film was one of a trio of projects presented at the reunion which are designed to bring the LBC studies to life outside of the scientific journal. Those attending the event were presented with a copy of the book LBC Lifetimes. The author Ann Lingard tells the stories of the lives and influences of participants and members of the team from the LBC studies. Also on display that day were a selection of portraits of participants and team members from the LBC studies painted by renowned portrait artist Fionna Carlisle as part of her project ‘Facing Age: Portrait of an Intelligent Scotland’. After the break, a second series of talks showcased the newest developments in the study. Dr Philippa Dall works with the Seniors USP (understanding Sedentary Patterns) group who are interested in the amount of time people spend sitting and lying down during the day. With the help of Philippa and her colleagues we will be adding this new aspect of research to the next wave of the LBC1936 study, more of which later.

From left to right: Prof.s Deay, Starr and

Wardlaw speaking at the LBC Reunion.

Ms Caroline Brett spoke next. Caroline works with Professor Deary on the 6-Day Sample and 36-Day Sample studies which assess individuals born on the first day of each alternative month of 1936, and the first 3 days of every month in 1936, respectively. Caroline was involved in clinic testing during the first two waves of the LBC1936 study. Next, Dr Tara Spires-Jones spoke about the valuable work the Edinburgh Brain Bank is doing, and about her particular interest in whether changes to the brain’s synapses (the parts of brain cells that allow information to be passed to each other) are responsible for memory decline. Finally, to wrap up this series of short talks, archivist Ms Emma Anthony from the Godfrey Thomson Project took to the stage. Emma has spent the last year cataloguing and preserving the papers of Professor Sir Godfrey Thomson, who was a central figure in the design and implementation of the Moray House Test which members of the LBC cohort sat at school at age 11 and during their assessments at age 70 and 76. More about Emma’s work can be found online at: http://libraryblogs.is.ed.ac.uk/godfreythomsonproject After this, there was a question and answer session which gave the audience a chance to ask Ian, John, and Study Co-ordinator Dr Simon Cox their questions. To close the day Ian spoke about the future of the project and our intention to call the participants of the LBC1936 study back in the coming summer. The event attracted the attention of the media, with coverage on the STV’s 6 o’clock news and the Scotland Tonight show on the same night. Footage from the day will soon be available on the LBC website: www.lothianbirthcohort.ed.ac.uk

The British Academy Debate: The Best Years of our Lives? Body, Brain and Well-being This exciting event closely followed the reunion, and was well attended. The lively and illuminating debate was also held at the General Assembly Hall in April. It was introduced with a short film by actor Simon Callow, and a piece from the evening’s chair, BBC Scotland news presenter and journalist Sally Magnusson. Both spoke candidly about their personal experiences of caring for close relatives with dementia. The panel, featuring Speakers Professor Ian Deary and Professor Catherine Ward Thompson from the University of Edinburgh, and Discussants Professor James Goodwin - Head of Research at Age UK, and Henry Simmons - Chief Executive of Alzheimer Scotland, went on to discuss questions including: what are the best years of our lives? How do our environments affect us as we age? And what can policy-makers do to improve the lives of older people? Film footage from the debate, including the film from Simon Callow, can be viewed on the British Academy website at: http://www.britac.ac.uk/events/2014/The_Best_Years_of_our_Lives.cfm

Prof. James Goodwin at the British Academy

Debate

Post-Wave 3 Questionnaire Before the next wave of the study begins in the summer, we are planning to send participants a short questionnaire to help us to investigate whether things like lifestyle and diet have changed over the years. It will also help us to investigate the effect that living environment - the places where participants have lived throughout their life - has on ageing. LBC1936 Study Wave 4! From late summer this year we plan to invite participants back for another wave of the LBC1936 study, their 4th assessment at the Wellcome Trust Clinical Research Facility (WTCRF). The continuing aim of the LBC1936 study is to investigate how people’s cognitive abilities (thinking and memory skills) change as they age, why people differ in the amount of change they experience, and what factors are associated with these changes. Without the ability to assess the same individuals on multiple occasions, (in the LBC1936 study at ages 70, 73 and 76 years old), we would not be able to answer these questions. Understanding Sedentary Patterns As part of our fourth wave of the LBC1936 Study we will be collaborating with the researchers in the Understanding Sedentary Patterns (USP) group. Participants will be asked if they would wear a small activity monitor (known as the activPAL) which will help us to understand the amount of time participants spend sitting, standing and walking as part of their usual daily life. The activPAL is about the size of a thin matchbox and is worn attached to the front of the participant’s thigh, under their usual clothes. The activPAL has been tried and tested on all members of the testing team, and was found to be extremely comfortable to wear.

News from Age UK At Age UK, we’re delighted to enrich our relationship with the CCACE through the Exchange Fellowship recently granted by the University of Edinburgh to Phil Rossall. Read more below, plus reflections on The Disconnected Mind project from Joey Vines and Helen Perry. Phil is Research Manager–Knowledge Management in Age UK’s Research Department. He sums up his role as making the latest statistics and research on ageing accessible to everyone. On a daily basis, he switches between hard facts and creative thinking on how best to exploit evidence to improve later life. The more the evidence generated by The Disconnected Mind, the more Phil’s mind has turned towards translation for social benefit. This was a main factor behind the joint Knowledge Exchange Plan for the project that Phil, Dr Robin Morton and others developed last year. The Exchange Fellowship was a logical next step. Phil said, “Robin and I saw it as an

Prof. Deary wearing his activPAL, just

about to get on his bike! Ian wore it for a

week and was fascinated to see how it

unobtrusively recorded his week’s activity.

opportunity to forge a more formal knowledge exchange bond between Age UK and CCACE. There are so many people who need to know about the findings from the project. It’s great to be working with Robin, and a privilege to be involved in making the results of such fantastic research available to the wide range of audiences accessible through Age UK’s networks. The next two years will be an exciting opportunity.”

Phil Rossall Other colleagues are equally inspired by The Disconnected Mind. Joey Vines, Senior Communications Officer in Group Communications, saw the recent launch of our new-look intranet as an opportunity to promote the project right across Age UK. He reflects on a memorable visit to Edinburgh. “The first time I heard about the project was during a meeting with Phil Rossall. The meeting was about something completely unrelated but, such is Phil’s enthusiasm for the project, we ended up chatting about it for a good half an hour, with Phil proclaiming that it is genuinely ground-breaking. I knew I had to find out more. So we set up an interview with Ian Deary, whom I visited in April. Ian and I spoke for a good 45 minutes about all things DMind – its origins, its progress, the role of the participants, its potential impact on society and much in-between. “As someone who doesn’t have a science background, I guess I’m representative of a lot of staff here at Age UK who may

have heard about the project but know little about its intricacies. Ian was very patient when responding to my questions, which enabled me to connect the dots and write a feature article based on my experience, which staff have responded well to. I’d like to thank Ian and his modest yet extremely knowledgeable team of experts for taking the time to talk me through the project. I look forward to seeing how things develop in the next few years and hope to report back to my colleagues on a more regular basis.” In the intranet, Joey’s article has ‘likes’ from teams as diverse as Training, Safeguarding and Retail. The interview has been adapted for the Age UK public website too: www.ageuk.org.uk/about-us/what-we-do/the-disconnected-mind/ Age UK raises funds to support The Disconnected Mind project from a wide range of charitable trusts and foundations. After her visit to Edinburgh in January this year, Helen Perry told us why The Lake House Charitable Foundation has been a supporter since 2007. “The Foundation’s main aims are to support children's charities and charities for the elderly. I set up the charity to enable me to really focus on these areas and make a real difference, rather than the random charitable giving that my husband Tim and I had done in the past. I also view the charity as a legacy I will leave my three children. “I first heard about The Disconnected Mind at an event at the Natural History Museum which we attended with my parents. My father was a Professor of Immunology and was fascinated by all research. He loved meeting Professor Deary! (Sadly my father passed away in 2012). The unique nature of the research and the fabulous opportunity it offered,

not only to Professor Deary and his team, but to wider society I found fascinating and I tell people the story often. I believe the findings are, and will continue to be, of global interest. “My visit to Edinburgh earlier this year confirmed my view. From meeting one of the Cohort to seeing the entire facility, I was impressed! It all came to life for me and made me even more committed to staying close to the research.” We are very grateful to all our generous donors. Read more about Helen and the Foundation’s work: www.thelakehouse.org.uk/index.html

Out and about with the DM team Gothenburg, Sweden: In May, Mrs Janie Corley and Dr Riccardo Marioni attended the 22nd Nordic Congress of Gerontology in Gothenburg, Sweden. Janie presented some of the data on the role of lifestyle factors in cognitive ageing in LBC1936. Riccardo presented some exciting new data on DNA methylation, cognitive ageing and mortality in both LBC cohorts. This Age UK special Gold Sponsor Symposium was chaired by Professor James Goodwin, Head of Research at Age UK Paris, France Dr Riccardo Marioni attended the Melodem (Methods in Longitudinal Research on Dementia Risk) meeting in Paris this May. He presented some of the LBC's most recent biological findings based on DNA-methlyation. Methylation is important in switching genes on and off. It also changes over the lifespan with certain genes being activated at different times. Recently, it has been shown to be an accurate predictor of age and thus a potential biomarker for biological ageing. In his presentation, Riccardo showed that

biological age, as predicted by methylation, was associated with an increased mortality risk. San Francisco, USA In May, Dr Stuart Ritchie attended the 26th Annual Association for Psychological Science Convention in San Francisco, California. He presented recent research using data from the LBC1936 on education and intelligence, as part of a symposium also featuring CCACE collaborators Prof. Timothy Bates (University of Edinburgh) and Dr Elliot Tucker-Drob (University of Texas at Austin) and with Dr Brian D’Onofrio (Indiana University) as a discussant. The symposium was well-attended, and the speakers discussed important issues relating to genetic and environmental influences on the development of cognitive ability across the lifespan. Visit from Professor Johannes Schroeder to the Lothian Birth Cohorts "Visit from an LBC Doppelganger...” On 10th April our Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE) was delighted to host a visit from Professor Johannes Schroeder of the Geriatric Psychiatry Department at the University of Heidelberg. He met with Ian Deary and his team, with CCACE PhD students and post-docs, and he gave an excellent seminar. He described his research aimed at understanding risk of cognitive decline and dementia. Much of it is based on birth cohorts from the previous East and West Germany, and born in 1930/32 and 1950/52. Now, that reminds us of something... He described the detailed work-up and follow-ups of the cohorts, which have been going on since 1993. He reckoned that about 20% of cognitive ability variance in older age could be obtained from: education, mental activity, social class, and physical activity.

He also has a keen interest in autobiographical memory. There was much CCACE interest in his concept of the 'golden days', meaning people's 20s. These were the years this people in his cohorts most liked to recall. The technical term for this is the 'reminiscence bump'; when's yours? One interesting result he'd found was that people with MCI can recall facts from their 'golden years' but not the 'stories'. Newly ‘in press’: how bilingualism helps the ageing mind A new paper by Dr Thomas Bak and LBC1936 team colleagues recently became available in Annals of Neurology and has attracted significant global coverage by the BBC (where it was the most shared online story), the New Scientist, The Times, The Sun, Huffington Post (most popular story), Time Magazine, CBS and Fox news channels, to name only a few. The paper suggests a positive effect of bilungualism (the

ability to speak more than one language) on later-life cognition, even when childhood intelligence was accounted for. This effect was even present for those who acquired their second language in adulthood. Other reports ‘in press’ Aribisala et al. (in press). Potential effect of skull thickening on the associations between cognition and brain atrophy in ageing. Age and Ageing. Bak et al. (in press). Does bilingualism influence cognitive aging? Annals of Neurology. Corley et al. (in press). Serum cholesterol and cognitive functions: the Lothian Birth Cohort 1936. International Psychogeriatrics. Cox et al. (in press). Correlational structure of ‘frontal’ tests and intelligence tests indicates two components with asymmetrical neurostructural correlates in old age. Intelligence. Deary (in press). The stability of intelligence from childhood to old age. Current Directions in Psychological Science. Ritchie et al. (in press). A strong link between speed of visual discrimination and cognitive ageing. Current Biology. Tang et al. (in press). Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function. PLoS One. Valdés Hernández et al. (in press). Differentiation of calcified regions and iron deposits in the ageing brain on conventional structural MR images. Journal of Magnetic Resonance Imaging,

Professor Johannes Schroeder meeting

with Professor Ian Deary at CCACE.

Newly Published in 2014: Benyamin et al. (2014). Childhood intelligence is heritable, highly polygenic and associated with FNBP1L. Molecular Psychiatry. Cox et al. (2014). A systematic review of brain frontal lobe parcellation techniques in magnetic resonance imaging. Brain Structure & Function. Davies et al. (2014). A genome-wide association study implicates the APOE locus in nonpathological cognitive ageing. Molecular Psychiatry. Hill et al. (2014). Functional Gene Group Analysis Indicates No Role for Heterotrimeric G Proteins in Cognitive Ability. PLoS ONE. Paterson et al. (2014). School reform and opportunity throughout the lifecourse: the Lothian Birth Cohort 1936. School Effectiveness and School Improvement.

Shenkin et al. (2014). The attitudes to ageing questionnaire: mokken scaling analysis. PloS One. Thomson et al. (2014). 708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects: analysis for association with psychiatric disorder and cognitive traits. Molecular Psychiatry. Zammit et al. (2014). Patterns and associates of cognitive function, psychosocial wellbeing and health in the Lothian Birth Cohort 1936. BMC Geriatrics.

You can stay up to date on the most recent DM research by checking the regularly-updated list of publications at: www.lothianbirthcohort.ed.ac.uk. Those requiring a PDF version of anything listed should get in touch with Paul Redmond (lbc1936@ed.ac.uk) in the first instance. Do also keep Paul updated about your ‘in press’ or recently published papers too. They’ll be added to the website to ensure everyone can see these as soon as possible, and may be profiled in a future newsletter. Contact Please get in touch with any items for inclusion in future newsletters.

Simon Cox

Simon.Cox@ed.ac.uk March 2014

www.lothianbirthcohort.ed.ac.uk