A genome-wide association study of non-pathological cognitive ageing

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Philosophy Psychology & Language

Abstract

There are growing proportions of older people in Western societies, and people are living longer. Therefore, the changes to the body that occur as people grow older have become a research priority. The changes that worry older people most are the changes to the brain. Cognitive decline--changes to thinking skills like memory, reasoning, and speed of thinking--is the most feared aspect of ageing. Cognitive decline is a major contribution to lower quality of life and lost independence in old age. In the United Kingdom, cognitive failure as the critical reason is the cause for 40% of admissions to institutional care. Cognitive impairment is a major personal and social burden both currently and in the future. Retaining cognitive functions must be a priority for older people and good research is needed to inform how this can be done. Cognitive ageing is far more than the medical conditions of dementia and mild cognitive impairment. The greater part of cognitive ageing occurs among otherwise healthy old people. This is known as 'normal, 'usual' and 'non-pathological' cognitive ageing. One of the more remarkable features of normal cognitive ageing is the range of effects. Some people decline quite markedly in thinking skills. whereas others retain these powers very well as they grow older. The aim of this project will be to try to find some of the clues to successful cognitive ageing, to why some people appear to have more cognitive reserve than others. There are a number of hints as to why some people's cognitive abilities show differences in ageing. There are physiological, lifestyle, and social contributions to the ageing of cognitive functions. The emphasis of the present project is on possible genetic contributions to the ageing of cognitive functions. It is important to appreciate that, to conduct such an investigation, it is important to have cognitive functions assessed on at least two occasions, many years apart. It is this aspect of the design that properly allows actual cognitive change to be studied. Few human studies have such data. For this project there will be two of the largest cohorts in the world with the correct cognitive information for such a study. There are about 2000 DNA samples from the University of Edinburgh. Among the subjects who provided these are those that have valid mental test data from the Scottish Mental Surveys of 1932 and 1947, at age 11, and have been tested on cognitive functions in old age. There are about 2000 DNA samples from the University of Manchester's Dyne Steele DNA bank. Again, these subjects are rare in having cognitive function data decades apart. In addition to these rare cognitive data, the cohorts have additional information on health, lifestyle, personality and brain imaging. There are 6000 replication samples available. Since 1998 over twenty genetic variants have been associated with cognitive ability. Unfortunately, a combination of small genetic effects and study populations have resulted in inconsistencies within the literature and confusion as to the whether or not a particular gentic variation is genuinely associated with cognitive ability. Far fewer studies, still, have information on genetic contributions to cognitive change within old age. The project will combine two of the largest and most informative elderly cognitive ageing cohorts in the world. A whole genome screen of their DNA will be conducted using the most up to date genetic testing platform to allow the most detailed screening of an elderly cohort for genes that influence cognitive ability and decline ever attempted. This data may provide invaluable information that could be used in the screening and treatment of cognitive impairment in the elderly. Genetic contributions to cognitive ageing do not imply something untreateable: genetic discoveries lead to understanding of mechanisms, which can lead to intervention. The study will provide definitive and therefore cost effective research.

Technical Summary

Cognitive ageing is the most feared aspect of growing old. It leads to lowered quality of life and loss of indendence. It is a huge financial burden to the nation. This involves not just the medical conditions of dementia and mild cognitive impairment but also the range of cognitive change that is referred to as normal, usual or nonpathological cognitive ageing. Understanding the contributions to variance in cognitive ageing is a research priority. The putative influences include medical conditions, fitness, lifestyle and psychosocial and demographic factors. There are also genetic contributions to individual differences in normal cognitive ageing, with variation in APOE among the best replicated. Although there is much interest in discovering the genetic contributions to cognitive ageing there are few appropriate data sets. That is, such a study requires large-enough samples with a rare phenotype: information on how cognition has changed across a sufficiently long period of time. In the present study we shall combine two of the largest cognitive ageing cohorts in the world with such data. There will be DNA and cognitive phenotypes from 2000 samples each at the University of Edinburgh and the University of Manchester. The University of Edinburgh has DNA and cognitive function data from people who took part in the Scottish Mental Survey of 1932 and 1947, at age 11, and were tested again 55-70 years later. The University of Manchester has DNA and cognitive function data in the Dyne Steele bank, with cognitive testing occurring over about 20 years. 4000 subjects' DNA will be subjected to whole genome screening using the Illumina Human370CNV chip. The top 30 SNPs (based on the association with cognitive ageing) will be tested on a further 6000 subjects in replication samples that are available in Scotland. The information from the replicated associations will provide unique information on the causes of cognitive ageing and may indicate paths to intervention.

Publications

10 25 50

 
Title LBC1936 Fast Facts Card 
Description Dr Simon Cox and Professor Ian Deary designed a 'Lothian Birth Cohort 1936 Fast Facts Card' - a 12 facet credit-card sized concertina leaflet containing information about the LBC1936 study for distribution to the general public at future KE events, interested academics / potential collaborators, LBC members etc. 
Type Of Art Artefact (including digital) 
Year Produced 2014 
Impact This has been distributed to interested academics and potential collaborators and will be distributed to participants in the Lothian Birth Cohort 1936. Age Scotland have requested 150 and an initial print run consisted of 2000 copies. 
 
Title Lifetimes book - Ann Lingard 
Description CCACE collaborated with a local author, Ann Lingard, to create a short book entitled 'Lifetimes - personal stories from the Lothian Birth Cohorts'. Ann interviewed several participants in both Lothian Birth Cohorts 1921 and 1936 and several members of staff, including the Centre director, creating this short collection of life stories. It has been professionally typeset with an attractive cover and introduction by CCACE/LBC director Ian Deary. It is heavily illustrated with photographs reflecting the life courses of the participants and scientists in the Lothian Birth Cohort studies. 
Type Of Art Creative Writing 
Year Produced 2014 
Impact The book has been sent to all CCACE collaborators and contacts, as well as being given out to participants at the Lothian Birth Cohort reunion in April 2014. It has been available to download as an e-book on various websites for many months. About 2000 physical copies of the book have been printed. It is free on iTunes, and there is a nominal cost (77p) on Amazon for a Kindle edition. 
URL https://itunes.apple.com/gb/book/lifetimes/id893954634?mt=11
 
Title Portraits - Fionna Carlisle 
Description CCACE has been collaborating with a local artist, Fionna Carlisle, who has painted portraits of the Centre director, Ian Deary, several of the Centre's staff, and a number of participants from the Lothian Birth Cohort studies. She is aiming to complete a collection of over 20 portraits of participants and scientists. 
Type Of Art Artwork 
Year Produced 2014 
Impact The artwork has been displayed at a number of prestigious local and national events, including as part of an exhibition at the British Library in London entitled Portraying Ageing on 28th April 2014, and at local events associated with the MRC Centenary. The CCACE knowledge exchange officer and Fionna Carlisle, along with Centre director Ian Deary, are in discussion with local art galleries and museums with regard to a full-scale exhibition of these portraits and the scientific programme of work which lies behind them. 
URL http://www.fionnacarlisle.com/
 
Description This project combines two of the largest and most informative elderly cognitive ageing cohorts in the world. A whole genome screen of their DNA was performed using the most up to date genetic testing platform to allow the most detailed screening of an elderly cohort for genes that influence cognitive ability and decline. This project has created a resource which combines detailed genetic information with an individual's cognitive ability and its age-related change, for approximately 3,500 individuals. This is an unusual resource as very few studies have detailed cognitive decline data over extended periods of time.One aspect of this project found that intelligence in old age is influenced by many genes each of which has a very small effect. We found that it is possible to predict intelligence, although with limited accuracy, from purely genetic information. We were also able to estimate the proportion of intelligence which is attributable to common variation observed in the genome. Using a similar method we were able to investigate genetic contributions to stability and change in intelligence from childhood to old age.We identified an association of the TOMM40/APOE region of chromosome 19 with cognitive decline. This region is known to be associated with Alzheimer's disease (AD). As part of this study we performed a detailed genetic analysis of this region of the genome which has long been associated with AD. The results of this analysis suggest that APOE has an effect on cognitive decline in healthy older individuals.We were the first group in the world to discover and publish that three genetic differences explain a lot of what makes people's blood clot in different times. Three genetic variants were found to explain ~18% of the variation in activated partial thromboplastin (aPTT) time, a measure of blood clotting time, in the Lothian Birth Cohorts. aPTT is associated with risk of thrombosis and coagulation disorders. This study has also made huge contributions to our knowledge of the genetic bases of bodily physiology and biochemistry through participation in more than 50 large genetic consortia. This has already led to many publications, summarized below, with many more in preparation.Summaries of consortia publications:Measures of lung function indicate respiratory health and are used in the diagnosis of respiratory disease. The effects of 2.5 million genetic variants on lung function measures were analysed in 48,000 individuals. Regions of the genome in or close to 16 genes were found to have an effect on lung function. These genes could be used to develop new drug targets for the treatment of respiratory diseases. Platelets are an essential part of the blood's clotting mechanism. The effects of 2.5 million genetic variants on platelet measures were analysed in 66,000 individuals. Sixty eight regions of the genome were found to be linked to these platelet measures. Animal models, zebra fish and fruit flies, were used for further investigation of these regions and 11 genes were found to play a role in blood cell formation.Previous studies have identified genetic variants which have an effect on blood pressure. In this study the effect of genetic variants on two further blood pressure measures, mean arterial pressure (MAP) and pulse pressure (PP). MAP is used to describe an average blood pressure in an individual and PP is defined as the amount of pressure required to create the feeling of a pulse. Seven new regions, in or close to genes, were found to have an effect on MAP (4), PP (2) or both of the measures (1). These results identified new biological pathways which influence variation in blood pressure. Variation in personality is predictive of many outcomes in life, including mental health. 2.5 million genetic variants were analysed for association with personality measures in approximately 17000 individuals. Personality measures used were Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. One gene, KATNAL2, was found to found to have an effect on conscientiousness, however a follow up analysis in a further 3000 individuals did not confirm this finding. Four genes previously reported to have an effect on early onset Alzheimer's disease and other neurodegenerative diseases were analysed for associations with risk of late onset Alzheimer's disease. Three of the genes studied were not found to contribute to the risk of developing late onset Alzheimer's disease. One gene, MAPT, was found to confer a possible risk, this finding requires further study.Genetic factors that influence success in bodily ageing are thought to also contribute to the successful ageing of mental abilities. Genes found to be linked to longevity in model organisms, yeast and nematodes, were investigated for association with mental ability in around 3500 older individuals and decline in this ability. One gene, SYNJ2, was found to be associated with mental ability in older individuals. Genetic influences on age at natural menopause were investigated in around 44,000 women. Four previously reported genomic regions and 13 new regions were found to be associated with age at menopause. Functions of the genes found in these regions include DNA repair and immune function. A pathway analysis method, used to identify groups of genes linked by function, identified new biological processes linked to timing of menopause.The white matter of the brain forms connections between the nerve cells. White matter integrity is a measure of the health of those connections. Variation at approximately 550,000 genetic markers was investigated for association with white matter integrity in around 500 older individuals. Suggestive links were reported with two genes (ADAMTS18 and LOC388630) however further work is required to confirm these findings. A pathway analysis method, used to identify groups of genes linked by function, identified biological processes - involving transmission of information and cell signaling - linked to white matter integrity measures.
The above was the text entered as of November 2013, this grant ended in 2011. The genetic data collected continue to be highly productive in high-impact scientific reports across many ageing-related and cognitive phenotypes. A full list of publications has been entered and credited to the grant. We foresee this resource continuing to be productive for several years. Some of the key recent papers involve cognition in older age. We are currently still contributing to several dozen genome-wide association consortia and leading several of them. We have enhanced the genome-wide single nucleotide polymorphism (SNP) data by adding genome-wide methylation data on the Lothian Birth Cohorts of 1921 and 1936. A series of cohort specific and consortium-based papers on epigenetic associations with important cognitive, ageing, and other phenotypes will appear and these will be credited to this BBSRC grant because the epigenetic papers will use the genetic information collected under its funding.
Exploitation Route Knowing the genetic contributions to people's differences in ageing, health, cognition, personality, mood, and other important well-being-related traits is of fundamental importance to medicine and the social sciences. This information, by contrast, informs how much of people's differences in these traits is affected by the environment. Also, knowing genetic associations allows access to mechanistic research on such traits and disorders. Far from being "determined" a genetic influence on a trait or disorder can lead to mechanistic information that can in turn lead to an intervention. We note that several of our studies from this grant have been taken up by the press in a positive way because they have thrown light on the fundamental basis of important human characteristics.
Sectors Communities and Social Services/Policy,Education,Healthcare

 
Description The findings from this project have contributed to the greater understanding of the genetic and environmental basis of important cognitive and other ageing-related phenotypes. This knowledge is being used to influence advisory strategy and government policy on ageing and cognition.
First Year Of Impact 2010
Sector Communities and Social Services/Policy,Education,Healthcare
Impact Types Policy & public services

 
Description Forum "Influencing the trajectories of ageing" - Ian Deary
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact The Academy of Medical Science brought together international experts on the influences on human and other animal ageing systems. These were presented in a forum conducted under Chatham House rules. There was an invited audience of about 60 experts in total. Each of the presentations-including Ian Deary's-was summarised and compiled in a report that was made available as an online PDF, communicated to the news media, and is intended to influence policy makers on the important issue of how to optimise the trajectories of human health across the full life course.
URL https://acmedsci.ac.uk/more/news/trajectories-of-ageing-balancing-longevity-and-health
 
Description Government Office for Science "Evidence and Options for Preserving Cognition Through Life" - Ian Deary
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL http://www.ccace.ed.ac.uk/node/336
 
Description ADRC - Scotland, ESRC
Amount £7,930,752 (GBP)
Funding ID ES/L007487/1 
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 11/2013 
End 10/2018
 
Description How do peripheral and central vascular markers relate to cognitive decline? - Deary
Amount £91,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2015 
End 01/2017
 
Description INTERpreting epigenetic signatires in Studies of Early Life Adversity (interSTELA) - Deary
Amount £199,512 (GBP)
Funding ID ES/N000382/1 
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 09/2015 
End 08/2017
 
Description MRC Integrated dementia research environment
Amount £6,825,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2015 
End 03/2016
 
Description MRC UK Dementia Platform
Amount £5,639,037 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2014 
End 03/2019
 
Description Project grant - JPND (Deary)
Amount £592,325 (GBP)
Funding ID MR/N027558/1 
Organisation Medical Research Council (MRC) 
Department MRC Human Nutrition Research Unit
Sector Public
Country United Kingdom
Start 05/2016 
End 04/2019
 
Description Seniors USP - LLHW
Amount £992,001 (GBP)
Organisation Medical Research Council (MRC) 
Department Lifelong Health and Wellbeing (LLHW)
Sector Public
Country United Kingdom
Start 05/2014 
End 04/2017
 
Title Liewald - CCACE cluster 
Description The CCACE computer cluster has been designed to allow it to deal with large GWAS datasets held by CCACE such as 1000G, exome sequencing and also the Generation Scotland reference genome sets. In conjunction with this are new file handling and merging techniques and pipelines which had to be developed to allow researchers to access and utilise these huge data resources. 
Type Of Material Biological samples 
Provided To Others? No  
Impact We have the capability of conducting, securely, large scale genetic analyses for our team and of allowing access to collaborators internationally. 
 
Description A genome-wide methylation study of human ageing - Sarah Harris 
Organisation University of Queensland
Department University of Queensland Diamantina Institute
Country Australia 
Sector Academic/University 
PI Contribution A collaboration with the University of Queensland, Australia entitled A genome-wide methylation study of human ageing was instigated at the end of 2012. LBC1936 and LBC1921 DNA samples were typed using the Illumina HumanMethylation450 BeadChip at the Wellcome Trust Clinical Research Facility (WTCRF). Quality control of the data was performed at the University of Queensland and analyses are ongoing at both CCACE and the University of Queensland. Both parties contributed financially to this project. CCACE contributed £300,000 and University of Queensland contributed £100,000.
Collaborator Contribution Quality control of the data and analyses are ongoing at both CCACE and the University of Queensland. Both parties contributed financially to this project.
Impact Several papers have been published.
Start Year 2012
 
Description GERAD consortium - GWAS of Alzheimer's disease 
Organisation Genetic and Environmental Risk in Alzheimer's Disease (GERAD)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution GERAD provided us with summary data from a large genome-wide association study of Alzheimer's Disease. From this we created polygenic risk scores for Alzheimer's disease in members of LBC1936, LBC1921, ABC1936 and the Manchester and Newcastle Longitudinal Studies of Cognitive Ageing.
Collaborator Contribution See above.
Impact The following publication has arisen: Harris SE, Davies G, Luciano M, Payton A, Fox HC, Haggarty P, Ollier W, Horan M, Porteous DJ, the Genetic and Environmental Risk for Alzheimer's Disease (GERAD1) Consortium, Starr JM, Whalley LJ, Pendleton N, Deary IJ (2014) Polygenic risk for Alzheimer's Disease is not associated with cognitive ability or cognitive aging in non-demented older people. Journal of Alzheimer's Disease. 39(3):565-74. doi: 10.3233/JAD-131058.
Start Year 2012
 
Description HALCyon 
Organisation HALCyon
Country United Kingdom 
Sector Academic/University 
PI Contribution The HALCyon collaborative research programme is funded by the UK Research Councils. From the Centre, Ian Deary, John Starr and Catherine Gale are PI's. The Centre receives funding from HALCyon. It is a consortium of ageing cohorts across the UK which has the aim of helping improve the lives of older people through better understanding of how healthy ageing is affected by social, psychological and biological factors acting across the whole of a person?EUR(TM)s life. It brings together an interdisciplinary group of scientists working on nine UK cohort studies to understand three main aspects of healthy ageing. The Edinburgh based Lothian Birth Cohort 1936 study forms one of the nine cohorts who contribute data.
Collaborator Contribution Data from the LBC 1936 and 1921 studies have contributed to the overall meta-analysis.
Impact Publications are emerging. The following papers have been published: 19864640 20214846 20843964 21225350 21297868 21332924 21349224 21542061 22114723 25073452 24563560 24365661 23922731 23894584. Further analyses are underway and publications are being prepared.
Start Year 2008
 
Description Human episodic memory - Davies/Deary 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Title: Integrated systems approach identifies genetic nodes and network for human episodic memory This collaboration is based in the UK. Genome-wide association analyses of memory phenotypes were performed on the Lothian Birth Cohorts in an attempt to replicate findings from a co-expression network analysis performed on human hippocampus samples.
Collaborator Contribution See above
Impact We were able to successfully replicate these findings and a manuscript has been submitted. This collaboration is multi-disciplinary, it involves genetics, psychology (cognition), genomic medicine, Clinical neurogenetics, and neurology.
Start Year 2014
 
Description Human episodic memory - Davies/Deary 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Title: Integrated systems approach identifies genetic nodes and network for human episodic memory This collaboration is based in the UK. Genome-wide association analyses of memory phenotypes were performed on the Lothian Birth Cohorts in an attempt to replicate findings from a co-expression network analysis performed on human hippocampus samples.
Collaborator Contribution See above
Impact We were able to successfully replicate these findings and a manuscript has been submitted. This collaboration is multi-disciplinary, it involves genetics, psychology (cognition), genomic medicine, Clinical neurogenetics, and neurology.
Start Year 2014
 
Description International genetics collaboration investigating runs of homozygosity (ROHgen) 
Organisation University of Edinburgh
Department Centre for Population Health Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution This is an international collaboration investigating the effects of runs of homozygosity on a number of health-related traits including cognition. Manuscript in preparation.
Collaborator Contribution This is an international collaboration investigating the effects of runs of homozygosity on a number of health-related traits including cognition. Manuscript in preparation.
Impact Manuscript published.
Start Year 2014
 
Description MAGIC - international glycaemic traits genetics consortium 
Organisation MAGIC
Country United Kingdom 
Sector Public 
PI Contribution The is an international glycaemic traits genetics consortium. Current work is focussed on analysis of exome chip data.
Collaborator Contribution The is an international glycaemic traits genetics consortium. Current work is focussed on analysis of exome chip data.
Impact Manuscript in preparation.
Start Year 2014
 
Description MRC Centre for Analysis in Translational Epidemiology 
Organisation University of Bristol
Department MRC Centre for Causal Analyses in Translational Epidemiology
Country United Kingdom 
Sector Public 
PI Contribution MRC CAiTE Director, Professor George Davey Smith from Bristol, invited Ian Deary begin_of_the_skype_highlighting     end_of_the_skype_highlighting and the CCACE to be a formal collaborator with his Centre.
Collaborator Contribution Formal collaborations have been made between the two Centres which has resulted in new research.
Impact Members from each Centre are collaborating on new research topics and have papers in preparation with some published (18994662 18704700). This collaboration has also resulted in the CHIC consortium: see separate entry. 25201988 23722424 23358156. Davey Smith and senior members of his team are providing the expertise for a CCACE special interest day in epigenetics in November 2014 and Davey Smith is giving the CCACE St Andrew's Day lecture in 2014.
Start Year 2009
 
Description MRC Integrative Epidemiology Unit in Bristol partnership - David Hill 
Organisation University of Bristol
Department MRC Integrative Epidemiology Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution My contributions to this were to supply data, as well as to assist in the interpretation and write up of the manuscript
Collaborator Contribution Perform the analyses, and to draft the manuscript.
Impact This has resulted in two papers submitted (Anderson, E. L., (2019) and Davies et al., (20019)). Both of these manuscripts utilise bivariate Mendelian randomisation to examine the unique effects education and intelligence have on Alzheimer's disease and a broad range of health and anthropometric variables.
Start Year 2017
 
Description Molecular genetic data to inform about the causes of socioeconomic differences - David Hill 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution David Hill leads a project aiming to use molecular genetic data to inform about the causes of socioeconomic differences.
Collaborator Contribution MRC Integrative Epidemiology Unit in Bristol performed a causal analysis using the data provided by David Hill. Karolinska Institutet, UCL Institute of Neurology in London, provided access to data on cell-type specific gene expression found in cortical tissues. NHS Blood and Transplant, Oxford and the National Institute for Health Research Blood and Transplant Unit in Donor Health and Genomics, University of Cambridge provided GWAS data.
Impact David Hill is currently working on corrections of the manuscript that details the project's findings.
Start Year 2017
 
Description Molecular genetic data to inform about the causes of socioeconomic differences - David Hill 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution David Hill leads a project aiming to use molecular genetic data to inform about the causes of socioeconomic differences.
Collaborator Contribution MRC Integrative Epidemiology Unit in Bristol performed a causal analysis using the data provided by David Hill. Karolinska Institutet, UCL Institute of Neurology in London, provided access to data on cell-type specific gene expression found in cortical tissues. NHS Blood and Transplant, Oxford and the National Institute for Health Research Blood and Transplant Unit in Donor Health and Genomics, University of Cambridge provided GWAS data.
Impact David Hill is currently working on corrections of the manuscript that details the project's findings.
Start Year 2017
 
Description Molecular genetic data to inform about the causes of socioeconomic differences - David Hill 
Organisation University of Bristol
Department MRC Integrative Epidemiology Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution David Hill leads a project aiming to use molecular genetic data to inform about the causes of socioeconomic differences.
Collaborator Contribution MRC Integrative Epidemiology Unit in Bristol performed a causal analysis using the data provided by David Hill. Karolinska Institutet, UCL Institute of Neurology in London, provided access to data on cell-type specific gene expression found in cortical tissues. NHS Blood and Transplant, Oxford and the National Institute for Health Research Blood and Transplant Unit in Donor Health and Genomics, University of Cambridge provided GWAS data.
Impact David Hill is currently working on corrections of the manuscript that details the project's findings.
Start Year 2017
 
Description Peter Visscher group - University of Queensland 
Organisation University of Queensland
Department Queensland Institute of Medical Research
Country Australia 
Sector Academic/University 
PI Contribution Provided cohorts with phenotypic data and genetic information, plus analysis. This was formally the collaboration with Queensland Institute of Medical Research.
Collaborator Contribution Provided cohorts with phenotypic data and genetics information, plus analysis.
Impact Publications have now arisen: PMIDs: 25249537, 25201988, 23732877, 23419543, 23358156, 23207651, 22832902, 22703881, 22700061, 22258510, 21826061, 1559497, 20303064, 19944402, 19290744, 19077176, 9077115, 18946731, 18493267, 24944428, 24554214, 23732877
Start Year 2008
 
Description University of Queensland - genome-wide methylation study 
Organisation University of Queensland
Country Australia 
Sector Academic/University 
PI Contribution LBC1936 and LBC1921 DNA samples were typed using the Illumina HumanMethylation450 BeadChip at the Wellcome Trust Clinical Research Facility (WTCRF). Quality control of the data was performed at the University of Queensland and analyses are ongoing at both CCACE and the University of Queensland.
Collaborator Contribution See above. Quality control of the data was performed at the University of Queensland.
Impact The following paper has been published: Shah S, McRae AF, Marioni RE, Harris SE, Gibson J, Henders AK, Redmond P, Cox SR, Pattie A, Corley J, Murphy L, Martin NG, Montgomery GW, Starr JM, Wray NR, Deary IJ, Visscher PM. (2014). Genetic and environmental exposures constrain epigenetic drift over the human life course. Genome Res doi:10.1101/gr.176933.114.
Start Year 2012
 
Description "Financial Abuse of Older People" - Stuart Ritchie 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Third sector organisations
Results and Impact February 18 2016: took part in a seminar on Financial Abuse of Older People at Age UK, alongside members of the police, policymakers, and charity workers.
Year(s) Of Engagement Activity 2016
 
Description 'AgeWell' annual event - Stuart Ritchie 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact September 1 2016: gave a talk on the LBC1936 to the 'AgeWell' annual event (general public audience) at the University of Birmingham.
Year(s) Of Engagement Activity 2016
 
Description Adam Smith Institute's 'Forum' event - Stuart Ritchie 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact December 3 2016: gave a talk on intelligence generally, including LBC1936 data, for the Adam Smith Institute's 'Forum' event (audience: general public).
Year(s) Of Engagement Activity 2016
 
Description Age UK Bake Sale 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact CCACE core staff and members help a bake sale in aid of Age UK in February 2016. The charity event was held in the Department of Psychology and was open to anyone who wanted to buy. Prizes were awarded for the cake that best linked to an area of research or study, and the most amusing design.
Year(s) Of Engagement Activity 2017
 
Description BBC1 television series "Holding back the years" 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Bill Turnbull, star of BBC's Breakfast News TV, Strictly Come Dancing, Classic FM etc., came to the Psychology department on 23rd January 2017 with a BBC film crew to find out about the Lothian Birth Cohort 1936 (LBC1936)/Disconnected Mind study.

BBC1 are planning a series in the Spring called 'Holding back the years'. Each programme will feature a celebrity revisiting a place that means a lot to them, and the programmes will have a focus on the processes of human ageing. Mr Turnbull was at the University of Edinburgh in the 1970's (he shared a flat with Gordon Brown for a term!), and so his programme is based here. It was natural that, to find out more about ageing, and with an Edinburgh locus, he and the BBC filming team visited the LBC1936. A busy afternoon's filming was filled with his interviewing LBC1936 Director Ian Deary, speaking with about a dozen of the LBC1936 participants, and seeing and taking part in some cognitive testing. Look out for the series, especially the Edinburgh-based Bill Turnbull programme in a few months' time.
Year(s) Of Engagement Activity 2017
URL http://www.ccace.ed.ac.uk/node/340
 
Description British Academy debate 29th April 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The Centre director, Ian Deary, presented the work of the Centre as part of a debate entitled The best years of our lives? on 29th April 2014. This was very well attended - around 300 people - and well publicised by the British Academy and beyond. The debate was chaired by well-known broadcaster Sally Magnusson (who recently wrote a book on dementia which had extended interviews with Ian Deary and John Starr), and also had contributions from Age UK's Professor James Goodwin, Alzheimers Scotland's Henry Simmons, and Professor Catharine Ward-Thompson.

The event was well publicised and recordings of the debate made available through social media and the British Academy website. There was a lively discussion after the debate.
Year(s) Of Engagement Activity 2014
 
Description Cox - Colinton Literary Society, Feb 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Simon Cox presented a talk entitled New Adventures in Cognitive Ageing Research: The Lothian Birth Cohorts of 1921 & 1936 at The Colinton Literary Society, Edinburgh, UK. February. (c.50 attendees).

The event was successful in disseminating information on the work of the Centre and Lothian Birth Cohort studies to members of the public.
Year(s) Of Engagement Activity 2014
 
Description Deary - British Academy Expert Workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact With CCACE fellow-elect, Dr Stuart Ritchie, Ian Deary obtained funding for and organised this British Academy-funded workshop on processing speed and its importance for cognitive ageing in humans held in April 2014. Among the 13 attendees were international experts from the USA, Europe and the UK. Also, Professor James Goodwin for Age UK attended in order to achieve knowledge exchange and impact for the discussions.


All of the discussions were audio recorded and slides made available. There were several impacts. First, Ian Deary and Stuart Ritchie wrote a summary article for British Academy Review and this made available the questions and discussion on processing speed to other academics. Second, Professor James Thompson of University College London extensively reported several of the talks with their Powerpoint slides on his much-read psychology blog, which reaches academics and lay people. Third, Professor James Goodwin took the results and their impact back to Age UK with a view to discussing how these were relevant to Age UK's aims in helping older people.
Year(s) Of Engagement Activity 2014
 
Description Deary - Glasgow Centre for Population Health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Invited seminar: Deary, I. J. (2014). Healthy cognitive ageing. Glasgow Centre for Population Health. Glasgow, UK, January. Ian Deary gave a talk on the follow-up studies of the Scottish Mental Surveys, especially the Lothian Birth Cohort studies of 1921 and 1936. It was described how these contribute to what we know about protective and risk factors for healthy cognitive ageing. The topic of dementia was also discussed. There was a lengthy question session afterwards and Professor Deary had drinks with the audience and had further discussion.

A video of the talk was placed on the GCPH website and has been viewed many times.
Year(s) Of Engagement Activity 2014
 
Description Deary - Healthy ageing LBC studies Inner Wheel Club Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Deary, I. J. (2014). Healthy ageing: clues from the Lothian Birth Cohorts of 1921 and 1936. The Inner Wheel Club of Edinburgh. Edinburgh, UK, February. Ian Deary gave a talk on the follow-up studies of the Scottish Mental Surveys, especially the Lothian Birth Cohort studies of 1921 and 1936. It was described how these contribute to what we know about protective and risk factors for healthy cognitive ageing. The topic of dementia was also discussed. There was a lengthy question session afterwards and Professor Deary took soup and sandwiches with the audience and had further discussion.

After this talk the organisers thought it was so important and successful that they passed on Professor Deary's details to other group organisers and subsequent invitations ensued.
Year(s) Of Engagement Activity 2014
 
Description Deary - Healthy cognitive ageing, York University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Ian Deary was invited to give a seminar on Healthy cognitive ageing at the University of York, October 2014.

Interest and enthusiasm shown by attendees, and increased knowledge of the work of the Centre and LBC studies. The host, Dr Gary Lewis, after discussion with Professor Deary, has established plans for a new collaboration with the Lothian Birth Cohort studies.
Year(s) Of Engagement Activity 2014
 
Description Deary - Leith Probus Club 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Invited talk: Deary, I. J. (2013). The Lothian Birth Cohort 1936. Leith Probus Club. Edinburgh, UK, October. Ian Deary gave a talk on the follow-up studies of the Scottish Mental Surveys, especially the Lothian Birth Cohort studies of 1921 and 1936. It was described how these contribute to what we know about protective and risk factors for healthy cognitive ageing. The topic of dementia was also discussed. There was a lengthy question session afterwards and Professor Deary took tea with the audience and had further discussion.

After this talk the organisers thought it was so important and successful that they passed on Professor Deary's details to other group organisers and subsequent invitations ensued.
Year(s) Of Engagement Activity 2014
 
Description Deary - MRC Network spring 2014 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact The MRC's publication, Network, published an article on Centre Director Ian Deary's workspace, which showcased the work of the Centre in spring 2014.

As is typical with these sorts of magazine-type articles, it attracted a lot of comment and attention, and many people, as a result, asked Professor Deary and colleagues about the history of the Scottish Mental Surveys and the work of the Lothian Birth Cohorts.
Year(s) Of Engagement Activity 2014
 
Description Deary - Pilrig St Paul's Guild, Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Invited talk: Deary, I. J. (2013). The Scottish Mental Surveys and healthy cognitive and brain ageing. Pilrig St Paul's Guild. Edinburgh, UK, November. Ian Deary gave a talk on the follow-up studies of the Scottish Mental Surveys, especially the Lothian Birth Cohort studies of 1921 and 1936. It was described how these contribute to what we know about protective and risk factors for healthy cognitive ageing. The topic of dementia was also discussed. There was a lengthy question session afterwards and Professor Deary took tea with the audience and had further discussion.

After this talk the organisers thought it was so important and successful that they passed on Professor Deary's details to other group organisers and subsequent invitations ensued.
Year(s) Of Engagement Activity 2014
 
Description Disconnected Mind newsletter - 2013+ 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact The Disconnected Mind project, which includes the Lothian Birth Cohort 1936 study and involves many of the Centre's members, produces a quarterly newsletter summarising study progress, impact and the latest research findings. This is distributed to approximately 126 funders and research collaborators across the UK.

The newsletter is sent to funders as well as research collaborators, and information on the study and its findings has been used by Age UK, the LBC1936 study's main funders, in their publications.
Year(s) Of Engagement Activity 2013,2014
 
Description Edinburgh International Science Festival 2014 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact CCACE held an interactive stall in the Museum of Scotland as part of the family drop-in activities at the Edinburgh International Science Festival 15th-19th April 2014. This was visited by over 2000 people over the course of the week, including Age UK's Chief Executive, Tom Wright. The stall and activities showcased the work of the Centre, particularly the Lothian Birth Cohort studies.

Children and parents were able to engage with many displays and objects relating to brain function and brain ageing. As in previous years many hundreds of people engaged with the Centre's representatives and illustrations of its work.
Year(s) Of Engagement Activity 2014
 
Description Frontiers BBC Radio 4 - LBC June 2014 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Results from the Lothian Birth Cohort studies were discussed by Ian Deary on BBC Radio 4's Frontiers programme, looking at the latest thinking about our brain power in old age. Robert Logie also discussed cognitive ageing on the programme.

The Lothian Birth Cohort studies were discussed alongside Cambridge studies and a provocative idea that there might be much less cognitive ageing than these studies suggest. As a result, there was discussion in the media, which reached the Centre, about the LBC studies.
Year(s) Of Engagement Activity 2014
 
Description HMC conference - Stuart Ritchie 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact October 4 2016: gave a talk on intelligence generally, including LBC1936 data, to the HMC conference (audience: headteachers) in Stratford
Year(s) Of Engagement Activity 2016
 
Description Hosting work experience pupils 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact CCACE hosted a series of work experience placements for pupils in s5/6 (secondary school). Pupils were given the opportunity to meet with CCACE members and observe some of the work of the Centre, including brain imaging, cognitive testing, and public engagement.

These placements were a great success, with several schools expressing an interest in sending pupils to the Centre for work experience in the future.
Year(s) Of Engagement Activity 2014
 
Description Life as a geneticist - Harris 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact A morning session talking to primary school children about life as a geneticist. The children made DNA models out of sweets and cocktail sticks (February 2016).
Year(s) Of Engagement Activity 2016
 
Description Lifetimes event at Midlothian Science Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Discussion session about the history and current research relating to the Lothian Birth Cohorts, and a showing of the short film The Living Brainabout the Lothian Birth Cohorts. Followed by hands-on reaction time testing and demonstration of brain images/3D printouts.
~30 members of the public attended a talk and a Q and A session.

A great deal of interest in the Lothian Birth Cohort studies and multiple Q andA sessions with a very engaged audience.
Year(s) Of Engagement Activity 2014
URL http://midlothiansciencefestival.com/event/lifetimes/
 
Description Lothian Birth Cohort reunion April 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact A reunion for participants in the Lothian Birth Cohorts of 1921 and 1936 was held on April 17th 2014 in Edinburgh. Presentations were given by main Principal Investigators and study co-ordinator on the results of the study to date, and short presentations were given on offshoot studies including the 6-Day Sample study and the MRC-funded Seniors USP study from which Dr Philippa Dall presented. There was also a premiere of the film "The Living Brain" made by Anne Milne.

Participants enjoyed the day and were interested and engaged in the information presented. They were given the opportunity to ask questions towards the end of the day and a great range of questions were received and answered. Talks from the reunion are on YouTube http://youtu.be/v1v7mHGkkgI
Year(s) Of Engagement Activity 2014
URL http://youtu.be/v1v7mHGkkgI
 
Description MRC Festival of Medical Research 2016 - Brain Maze event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact In June 2016 CCACE opened its doors to the public for the second outing of our popular Brain Maze event. CCACE joined forces with the Centre for Regeneritive Medicine to put on the interactive open day event as part of the Medical Research Council's Festival of Medical Research.

The sell out event (around 50-60 people took part in some way) led people through the maze of corridors and rooms in the basement of the Department of Psychology, where CCACE is based. In each of the 11 rooms, the had 10 minutes to experience a different aspect of the ageing brain and body. Popular activities included a supermarket sweep game, shopping for the lifestyle factors which affect how our brain ages (like smoking) while busting a few myths (like the lack of effect of brain training). The Maze finished with a cafe where participants got the chance to speak with scientists and reflect on their experience of the Maze. One of the main comments was that, having spent 2 hours in the maze chatting to scientists, people would have liked more time in each room. A great endosement of the time and effort invested by CCACE and CRM staff and students.
Year(s) Of Engagement Activity 2016
URL http://www.ccace.ed.ac.uk/news-events/latest/maze2
 
Description National Museum of Scotland Science Saturday 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact October 2016: "Science Saturday" event at the National Museums of Scotland showcases gene science and the impact and relevance of our research to human health and society.

The Science Saturday event was open to all, with a mini-symposium and debate session, in addition to a Market Place event held in the main hall area. Stands representing the Institute of Genetics and Molecular Medicine, the MRC Centre for Cognitive Ageing and Cognitive Epidemiology, Generation Scotland, the Wellcome Trust Clinical Research Facility Genetics Core, Edinburgh Genomics, the Usher Institute, the Mason Institute for medicine, life-sciences and the law, the Institute for the study of Science, Technology and Innovation and the MRC Farr, Edinburgh all set up shop to describe their take on gene science and the impact and relevance to human health and society.

The talk and exhibition sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2016
URL http://www.ed.ac.uk/centre-genomic-medicine/news-events/news-2016/science-saturday
 
Description Professor Sir Godfrey Thomson exhibition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact A treasure trove of artefacts relating to this pioneering educational psychologist will be displayed at the Univeristy of Edinburgh from Friday 29th July until 29th October. Entrance to the exhibition is free, and it is open to the public.

Piles of intriguing ledgers and personal mementos will feature in an exhibition reconstructing the life and work of Professor Sir Godfrey Thomson. Sir Godfrey - who led the world's only nationwide IQ tests, in Scotland - was an innovative educator who firmly belived that educational opportunity should not be linked to social staus. From the 1920s onwards he advocated comprehensive education. Thomson was based at the Moray House School of Education, now part of the University of Edinburgh. His greatest legacy for today's researchers was to test the intelligence of almost every Scottish 11-year-old child in 1932, and again in 1947.

For the first time, the Scottish Mental Survey's unique ledgers will go on public view, with a selection of sample pages on show. The ledgers hold the world's only record of IQ-type scores from full national year-of-birth cohorts.

Sir Godfrey's findings have formed the basis of much of the cutting-edge research at the University of Edinburgh since the late 1990's into how the brain ages, led by Professor Ian Deary. His team studies the now-older people who took part in the Scottish Mental Surveys.

Ian has spent the past decade investigating Sir Godfrey's life, and in 2008 he rescued a mass of never-before-seen documents and objects from Thomson's family home in Edinburgh, just before it was demolished. A selection of those artefacts, portraits and documents feature in the exhibition, telling the story of who Sir Godfrey was and what his motivations were.

Ian Deary said: "Godfrey Thomson saw mental ability tests as an imperfect but useful means to give poor children a chance in life. He was determined to look past pupils' social status, and try to see their underlying ability. By all accounts he was modest, not motivated by money, and happy to share academic wins, which in part led him to fade from the history books. I'm delighted we are now able better to understand and evaluate the pioneering work of this multi-talented and elusive man."

8103 individuals visited the exhibition.
Year(s) Of Engagement Activity 2016
URL http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-36894717
 
Description Ritchie - Infinite Monkey Cage, August 2014 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Centre member Stuart Ritchie participated as a panelist on BBC Radio 4's Infinite Monkey Cage programme, broadcast on 11 August 2014. In this, Ritchie discussed the nature, causes and consequences of people's intelligence differences, showcasing the work of the Centre and discussing causes of people's differences in cognitive ageing.

This programme has a large audience and the Centre's work on cognitive abilities and cognitive ageing will have been heard by a large number of people.
Year(s) Of Engagement Activity 2014
 
Description STV coverage - LBC reunion 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact The LBC reunion, organised and facilitated by CCACE, was covered on STV news on 17th April 2014.

XXX
Year(s) Of Engagement Activity 2014
 
Description Science Magazine article 31st October 2014 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact The work of the Centre, in particular the Lothian Birth Cohorts, was featured in a 4-page article in Science Magazine by Emily Underwood. This was published on 31st October 2014 and promoted through various social media outlets.

It is very unusual to have the world's top general science journal devote four pages to a single set of studies, i.e. our Lothian Birth Cohort studies. The prominence of this story meant that we obtained large numbers of national and international contacts indicating that they had seen and enjoyed the report, and wanted to know more about the studies.
Year(s) Of Engagement Activity 2014
URL http://www.sciencemag.org/content/346/6209/568.summary