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 34: June 2016 Welcome to the Spring Disconnected Mind newsletter of 2016. As always, this issue includes some of our recent publications, the regular contribution from our colleagues at Age UK, and news and reports from recent events. Please get in touch for more information about anything in the newsletter, particularly if you have something you would like to be included in a future issue. Contact details can be found on the last page. LBC1936 Study Update – Wave 4 Data collection from LBC1936 participants for Wave 4 is currently ongoing. As of 1st June 2016, we have had the usual superb response from LBC1936 cohort members. We have seen 446 participants at the Wellcome Trust Clinical Research Facility, completing cognitive and physical tests for a fourth time, at about age 79. So far, 288 have already completed a brain MRI scan and 373 have completed a Doppler ultrasound of their carotid arteries. We are delighted to announce that we have completed the Seniors Understanding Sedentary Patters feature of the study. In that, 302 LBC participants have completed diaries documenting their activity and worn the activPAL activity monitor. This has been incredibly well received by the LBC cohort members. We will be looking at how activity and sedentary behaviour interact with a variety of difference factors in ageing.

Phase 3 begins Professor Deary and the team are proud to announce that the Disconnected Mind project entered its 3rd Phase of its funding from Age UK, as of 1st April 2016! Ian said, “it is fantastic to continue our longstanding, productive and successful relationship with Age UK”. With this new chapter of the project beginning, it opens doors to further research related to the 8th decade of life in the LBC1936 cohort. The future holds great possibilities with this project’s prolific contributions to ageing research.

WELCOME

TO PHASE 3!

LBC Milestone- Sequencing the future Edinburgh Genomics, a leading UK clinical genomics facility within the University of Edinburgh, has completed the sequencing of over 1300 whole genomes of the Lothian Birth Cohorts. This means that, for each person in the cohorts, the scientists will know the three billion or so base pairs that make up their DNA sequence.

Ian, said, “The Lothian Birth Cohorts are a uniquely valuable group of people whose life-long data from childhood to older age has helped us understand healthy cognitive ageing and wellbeing across the life course. Some of the LBC have been followed across 80 years. We are delighted that, with funding support from the Biotechnology and Biological Sciences Research Council (BBSRC) and the excellent service provided by Edinburgh Genomics, we have managed to sequence the entire genomes of a large number of individuals from the cohort so quickly. Such a massive undertaking on so many people in a single cohort would have been unthinkable just a few years ago. This genome sequence data will prove invaluable for understanding why some people’s brains and thinking skills age better than others. The flip side of having such comprehensive genetic data is that we will also understand better how the environment and lifestyles contribute to healthy ageing.”

A video of the DNA Sequencing and commentary by Prof Deary can be found via the link below: https://youtu.be/-kWyZPuYkyk Associates of white matter damage and ageing The Disconnected Mind project’s discoveries relating to the brain continue to flourish. Of note, research by Dickie et al. (reported in the journal Neurobiology of Aging) explored factors that are important in determining damage to the brain’s white matter (connecting fibres). This white matter damage is a common feature of the ageing brain. The degree of this damage, is frequently measured as the volume of white matter hyperintensities (or scar-like lesions), which are observable on MRI images of the brain. Those with a greater volume of white matter hyperinensities are more likely to suffer from cognitive decline, dementia, or stroke. Using MRI brain scans of the Lothian Birth Cohort 1936 taken three years apart, at age 73 and 76, Dickie et al. measured the increase in the amount of white matter hyperintensities. Then they looked for factors that predicted this change, examining many risk factors such as smoking status, blood pressure, high-density (‘good’) cholesterol level, diabetes, cardiovascular disease and Body Mass Index. Out of all of these, only two factors were associated with an increase in white matter hyperintensity volume between the age 73 and 76. These harmful factors were being a current smoker and having a lower level of the high-density cholesterol. These findings add to the emphasis that various lifestyle factors, such as smoking cessation and cholesterol level control, might be important in conserving brain healthy as individuals age.

Prof Deary loading the last samples to complete the LBC whole genome sequencing

Poetic Justice Below is an elegant and excellent poem that we at the Disconnected Mind project would like to share. It written by one our own LBC1936 cohort members about their experience during their brain imaging visit:

Staff News Following on from achievements reported in the previous newsletter, we are delighted to announce that Ciara Madden, Research Assistant on the Disconnected Mind project, has successfully passed her MSc by Research, looking at resilience in older age in the LBC cohorts Ratko Radakovic, the LBC1936 Study Co-ordinator has defended his PhD successfully, passing his PhD viva with only minor corrections. The thesis was entitled ‘Multidimensional Apathy in Neurodegenerative Diseases’ and looked at different profiles of apathy/demotivation in healthy and pathological ageing, as well as how apathy subtypes associate with disease stage, activities of daily living and cognitive dysfunction. Congratulations Dr Radakovic! Stroke Association’s Keynote Lecture Professor Joanna Wardlaw, the project’s leader for neuroimaging, gave the Stroke Association’s Keynote Lecture in April 2016. It was on ‘One small vessel stroke? One giant problem for humankind’. It was held in the grand surroundings of Lancaster House in London, commissioned by the Duke of York in 1825 and nowadays managed by the Foreign & Commonwealth Office. The Keynote lecture cited a variety of LBC cohort findings, showing the importance and impact of the DM mind project to the general public. Sir Mark Walport, Government Chief Scientific Adviser and Head of the Government Office for Science was in attendance and described the Lecture as “tremendous” and commented that it showed the importance of research to tackling the problems that we face today. Prof Wardlaw’s lecture can be seen online via the link below: https://www.stroke.org.uk/news/keynote-lecture-2016

Photo Opportunity

Just keep your trousers on, she softly said,

and put your watch and coins in that wee bin.

Here, let me help you get up on the bed.

You must stay still, so I’ll just wedge you in.

You’ll hear some noise, so put these in your

ears.

OK? A button pressed, and in I went.

For ninety minutes, lost souls, ghouls,

banshees,

off-key sopranos, an avant-garde quartet:

satanic cacophonics filled my head—

a diabolic prom for the insane;

and then, they stopped. Weird silence there

instead,

and now they’ve got five pictures of my brain.

What will they see? The scars of guilt and

shame

and love? Or things that don’t yet have a

name?

Tom Sommerville

Growth of white matter hyperintensities from 73 (Blue) to 76 years (Red) of age

Dementia Platform UK conference The Dementias Platform UK had their annual conference in London at the end of April 2016. The LBC1936 cohort is a contributing member to Dementia Platforms UK initiative, helping to further research to better understand ageing (both healthy and pathological). Part of the conference included a showcase of the work of early careers researchers. The Dementias Platform UK executive committee selected three early career researchers to give a presentation in front of the 300 guests, including many distinguished researchers in the field of dementia research. The prize for best presentation was awarded to Chloe Fawns-Ritchie, from our CCACE centre who presented on her work developing an enhanced cognitive assessment that will be used to better understand cognitive decline and the development of dementia in the UK Biobank study. Chloe said, ‘It was a fantastic, though nerve-wracking, experience to be able to present in front of some of the world leading experts in dementia research. I enjoyed being able to show others the work that I have been carrying out in the last 18 months, and I received some really positive feedback on my work.’

LBC contributions to Generation Scotland and STRADL The 6th and 9th of May 2016 saw, back to back (if you ignore the weekend) annual meetings of the large Generation Scotland (GS) and STRADL (Stratifying Depression Longitudinally) research programmes in Edinburgh. Both saw good attendance by Lothian Birth Cohort staff. Professor Ian Deary is the Chair of the Cognitive Expert Working Group on GS, and he is a Co-Principal Investigator on STRADL. Ian presented the GS cognitive research at the GS day, much of which included genetics, and explained how closely the GS and LBC samples enhance each other's research, often being used to replicate results. On the STRADL day, Saskia Hagenaars, a PhD student in our team, described her research that investigated cognitive functions and their genetic associations with health. Again, Saskia clearly showed how LBC data work together with GS and UK Biobank data to provide valuable replications. Post-doctoral fellows Stuart Ritchie and Riccardo Marioni, respectively, presented LBC data on resilience and epigenetics to the STRADL conference. Ian said, "Well, it is back to work now after these two invigorating days. The Disconnected Mind/Lothian Birth Cohort is our golden ticket to the high table of these large projects' research programmes. The cutting edge work in LBC keeps us ahead internationally and people look to the team for new results and for a high-quality check for their own results." On the day of the STRADL meeting, Ian also made a surprise visit to the Welcome Trust Clinical Research Facility and met up with LBC1936 cohort members, Mrs Catherine Harris and Mrs Elizabeth Stewart—identical twins, no less!— who were undergoing cognitive testing in the same venue as the conference.

Prof Wardlaw giving the Keynote lecture

to an engaged audience

Telling U3A about Healthy Cognitive Ageing On 17th March Professor Ian Deary spoke to the Science Group of the University of the Third Age at Epworth Halls in Edinburgh. The topic was Health Cognitive Ageing, with the focus on how the Lothian Birth Cohorts and Disconnected Mind project had contributed. "They were an attentive and active audience", said Ian. "I talked for about 50 minutes and there was well over half an hour of questions, with no signs of that slowing when the Chair had to intervene and let people get home.” Dr Peter Edwards afterwards wrote to Ian, "your insights into the factors which affect cognitive decline, and those which don't, were particularly interesting. The audience was bigger than expected; it was, in fact, by far the largest audience that we have ever had at one of our talks." About 30 to 40 were expected; there were, in fact, about 100 people there. Godfrey Thompson Exhibition This summer will see a new exhibition honouring the life and work of Professor Sir Godfrey Thomson, an Educational psychologist contributing vastly to intelligence research. He created the Moray House Test that was used in the Scottish Mental Surveys, and made possible the Disconnected Mind project and, therefore, the LBC studies.

The exhibition will be hosted at the University of Edinburgh’s Main Library and will be open to the public from the 29th July for 3 months. News from Age UK We’re sure that you’re as excited and delighted as we are that the Age UK Trustees’ Board has agreed to continue supporting The Disconnected Mind project for a third phase, for the next three years. The decision was based on a number of factors, not least the significance of the project to Age UK’s strategic priorities, the excellent progress and outputs that you continue to achieve in the research and the comprehensive plans for a Phase 3 that Ian Deary described to us and that our independent referees resoundingly endorsed. Reflecting the decision, our CEO Tom Wright wrote to Ian at the end of March, “We wish you and your team every success in continuing your outstanding work through Phase 3 and look forward to enjoying further co-operation with you on a range of activities relating to the project. We are very pleased to continue our support and our excellent relationship with you.” At the same time, we have been undergoing some changes here at Tavis House. In the time we’ve known you, the

Prof Deary with our twin LBC1936 cohort members

Professor Sir Godfrey Thomson

Age UK Research team has been headed by Professor James Goodwin. Effective from 1st April, James has been appointed to the newly-created role of Chief Scientist with, among other things, an enhanced remit of developing our health work overseas with our sister charity, Age International. The Research team has consequently merged with the Policy team, whose role is influencing government and other key stakeholders on a wide range of age-related issues. These include housing, transport and communities; income, pensions, benefits and poverty; energy and other utilities; work, employment and learning; scams, fraud, human rights, equalities, discrimination and more. Jane Vass is Director of the newly-formed Policy and Research Department. We will introduce you to Jane and other team members in future newsletters. As usual, we have not been idle on research. Last year, the Research team and Health Influencing team were commissioned by the Department of Health to carry out a survey of the provision of dementia adviser services across England. We worked with Ipsos MORI to deliver the project and the report was published in April: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/513191/Dementia_Advisers_Full_Report.pdf One of our team members, Social and Economic Research Manager Marcus Green, has been particularly far from idle. He ran this year’s Virgin London Marathon – his 7th marathon worldwide – in a very speedy 2 hours 45 minutes and 51 seconds, somewhat faster than our CEO Tom Wright’s 4 hours and 32 minutes. Congratulations Marcus and Tom!

DMind publications Newly ‘in press’ Deary, I. J., Cox, S. R., & Ritchie, S. J. (in press). Getting Spearman off the skyhook: one more in a century (since Thomson, 1916) of attempts to vanquish g. Psychological Inquiry. Dykiert, D., Der, G., Starr, J. M., & Deary, I. J. (in press). Why is mini-mental state examination performance correlated with estimated premorbid cognitive ability? Psychological Medicine.

Okbay, A., 192 authors, Deary, I. J., 68 authors, Benjamin, D. J. (in press). Education-associated SNPs are enriched for brain function and disorders. Nature. E-published ahead of print. Hagenaars, S. P., Harris, S. E., Davies, G., Hill, W. D., Liewald, D. C. M., Ritchie, S. J., … Deary, I. J. (in press). Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia. Molecular Psychiatry. doi:10.1038/mp.2015.225 Howrigan, D. P., Simonson, M. A., Davies, G., Harris, S. E., Tenesa, A.,

Marcus Green at marathon pace

Starr, J. M., … Keller, M. C. (2015). Genome-wide autozygosity is associated with lower general cognitive ability. Molecular Psychiatry. doi:10.1038/mp.2015.120 Kuznetsova, K. A., Maniega, S. M., Ritchie, S. J., Cox, S. R., Storkey, A. J., Starr, J. M., … Bastin, M. E. (in press). Brain white matter structure and information processing speed in healthy older age. Brain Structure & Function. doi:10.1007/s00429-015-1097-5 Lewis, G. J., Cox, S. R., Booth, T., Maniega, S. M., Royle, N. A., Hernández, M. V., … Deary, I. J. (in press). Trait Conscientiousness and the Personality Meta-Trait Stability are Associated with Regional White Matter Microstructure. Social Cognitive and Affective Neuroscience. doi:10.1093/scan/nsw037 Mõttus, R., Marioni, R., & Deary, I. J. (in press). Markers of Psychological Differences and Social and Health Inequalities: Possible Genetic and Phenotypic Overlaps. Journal of Personality. doi:10.1111/jopy.12220 Newly ‘in print’ Broer, T., Pickersgill, M., & Deary, I. J. (2016). The Movement of Research from the Laboratory to the Living Room: a Case Study of Public Engagement with Cognitive Science. Neuroethics, 1–13. doi:10.1007/s12152-016-9259-6 Deary, I. J., & Ritchie, S. J. (2016). Processing speed differences between 70- and 83-year-olds matched on childhood IQ. Intelligence, 55, 28–33. doi:10.1016/j.intell.2016.01.002 Dickie, D. A., Ritchie, S. J., Cox, S. R., Sakka, E., Royle, N. A., Aribisala, B. S., Valdes Hernandez, M., Maniega, S. M., Pattie, A., Corley, J., Starr, J. M., Bastin, M. E., Deary, I. J., & Wardlaw, J. M. (2016). Vascular risk factors and progression of white matter hyperintensities in the Lothian Birth

Cohort 1936. Neurobiology of Aging, 42, 116–123. doi:10.1016/j.neurobiolaging.2016.03.011 Harris, S. E., Malik, R., Marioni, R., Campbell, A., Seshadri, S., Worrall, B. B., … METASTROKE Consortium. (2016). Polygenic risk of ischemic stroke is associated with cognitive ability. Neurology, 86, 611–618. doi:10.1212/WNL.0000000000002306 Kim, J., Valdés Hernández, M. D. C., Royle, N. A., Maniega, S. M., Aribisala, B. S., Gow, A. J., … Park, J. (2016). 3D shape analysis of the brain’s third ventricle using a midplane encoded symmetric template model. Computer Methods and Programs in Biomedicine, 129, 51–62. doi:10.1016/j.cmpb.2016.02.014 Lin, Q., Weidner, C. I., Costa, I. G., Marioni, R. E., Ferreira, M. R. P., Deary, I. J., & Wagner, W. (2016). DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy. Aging, 8, 394–401. Pearce, J., Shortt, N., Rind, E., & Mitchell, R. (2016). Life Course, Green Space and Health: Incorporating Place into Life Course Epidemiology. International Journal of Environmental Research and Public Health, 13. doi:10.3390/ijerph13030331 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 with your ‘in press’ or recently published papers. 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.

Ratko Radakovic

r.radakovic@ed.ac.uk June 2016

www.lothianbirthcohort.ed.ac.uk