"The National Hospital for the Relief and Cure of Paralysis and Epilepsy, as it was first named, was founded in November 1959, and opened its doors for business in 1860 as the first specialist neurological hospital in the world. It quickly gained a reputation as the 'mecca of neurology' and soon became a place of pilgrimage for neurologists from many countries. This book celebrates the fluctuating fortunes, and fascinating history from foundation to eventual amalgamation of the National Hospital with University College Hospital in 1996, and its Institute of Neurology with University College London in 1997"--
INTRODUCTION: Barriers to recruitment for dementia studies are well documented. As part of the UK government's Dementia 2020 strategy, a nationally consistent system to increase public engagement and participation in research was launched in February 2015. METHODS: We describe the development of the "Join Dementia Research" registry, including evolution of policy, involvement of people with dementia in co‐production, data requirements, governance, technology, and the impact on study recruitment and what factors may have contributed to the services success. RESULTS: The UK‐wide online, telephone, and postal service has registered 47,071 volunteers, with 33,139 people (67.9% of all volunteers) taking part in 378 studies, with 49,954 total study enrolments. This has taken place across 295 research sites, involved 1522 researchers, and resulted in 134 peer‐reviewed publications. DISCUSSION: Public registries of individuals interested in research, with user‐provided data enabling basic phenotyping, are effective at increasing public engagement with research and removing barriers to study recruitment. Deeper pheno/genotyping could be undertaken to improve matching, but how and when that information is collected will be a key factor.
Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer's disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer's disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer's disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer's disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer's disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer's disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer's disease showed early hippocampal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion. Cognitive models showed tests sensitive to visuospatial dysfunction declined earlier in posterior cortical atrophy than typical Alzheimer's disease whilst tests sensitive to working memory impairment declined earlier in typical Alzheimer's disease than posterior cortical atrophy. These findings indicate that posterior cortical atrophy and typical Alzheimer's disease have distinct sites of onset and different profiles of spatial and temporal progression. The ordering of disease events both motivates investigation of biological factors underpinning phenotypic heterogeneity, and informs the selection of measures for clinical trials in posterior cortical atrophy. ; This work was supported by an Alzheimer's Research UK Senior Research Fellowship and ESRC/NIHR (ES/L001810/1) and EPSRC (EP/M006093/1) grants to S.J.C. K.Y. is funded by the Alzheimer's Society. The Dementia Research Centre is supported by Alzheimer's Research UK, Brain Research Trust, and The Wolfson Foundation. This work was also supported by the NIHR Queen Square Dementia Biomedical Research Unit, and the NIHR UCL/H Biomedical Research Centre. N.F. is funded by EPSRC (EP/M006093/1). R.V.M. was supported by the EPSRC Centre For Doctoral Training in Medical Imaging with grant EP/L016478/1. R.W.P. is an NIHR Academic Clinical lecturer. J.M.S. acknowledges the support of the Wolfson Foundation, EPSRC (EP/J020990/1), MRC (MR/L023784/1), ARUK (ARUK-Network 2012–6-ICE; ARUK-PG2017–1946), Brain Research Trust (UCC14191) and European Union's Horizon 2020 research and innovation programme (Grant 666992). T.J.S. was supported by an Alzheimer's Research UK Research Fellowship. J.W. was supported by funding from the Alzheimer's Society and the NIHR UCLH Biomedical Research Centre. Some authors (N.P.O., S.O., D.C.A., and J.M.S.) acknowledge funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 666992. The work was also supported by funding from National Institutes of Health R01-AG045611 (to G.D.R.), P50-AG23501 (to B.L.M. and G.D.R.)
The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
In: Bauermeister , S , Orton , C , Thompson , S , Barker , R A , Bauermeister , J R , Ben-Shlomo , Y , Brayne , C , Burn , D , Campbell , A , Calvin , C , Chandran , S , Chaturvedi , N , Chêne , G , Chessell , I P , Corbett , A , Davis , D H J , Denis , M , Dufouil , C , Elliott , P , Fox , N , Hill , D , Hofer , S M , Hu , M T , Jindra , C , Kee , F , Kim , C H , Kim , C , Kivimaki , M , Koychev , I , Lawson , R A , Linden , G J , Lyons , R A , Mackay , C , Matthews , P M , McGuiness , B , Middleton , L , Moody , C , Moore , K , Na , D L , O'Brien , J T , Ourselin , S , Paranjothy , S , Park , K S , Porteous , D J , Richards , M , Ritchie , C W , Rohrer , J D , Rossor , M N , Rowe , J B , Scahill , R , Schnier , C , Schott , J M , Seo , S W , South , M , Steptoe , M , Tabrizi , S J , Tales , A , Tillin , T , Timpson , N J , Toga , A W , Visser , P J , Wade-Martins , R , Wilkinson , T , Williams , J , Wong , A & Gallacher , J E J 2020 , ' The Dementias Platform UK (DPUK) Data Portal ' , European Journal of Epidemiology , vol. 35 , no. 6 , pp. 601-611 . https://doi.org/10.1007/s10654-020-00633-4
The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
In: Bauermeister , S , Orton , C , Thompson , S , Barker , R A , Bauermeister , J R , Ben-Shlomo , Y , Brayne , C , Burn , D , Campbell , A , Calvin , C , Chandran , S , Chaturvedi , N , Chêne , G , Chessell , I P , Corbett , A , Davis , D H J , Denis , M , Dufouil , C , Elliott , P , Fox , N , Hill , D , Hofer , S M , Hu , M T , Jindra , C , Kee , F , Kim , C H , Kim , C , Kivimaki , M , Koychev , I , Lawson , R A , Linden , G J , Lyons , R A , Mackay , C , Matthews , P M , McGuiness , B , Middleton , L , Moody , C , Moore , K , Na , D L , O'Brien , J T , Ourselin , S , Paranjothy , S , Park , K S , Porteous , D J , Richards , M , Ritchie , C W , Rohrer , J D , Rossor , M N , Rowe , J B , Scahill , R , Schnier , C , Schott , J M , Seo , S W , South , M , Steptoe , M , Tabrizi , S J , Tales , A , Tillin , T , Timpson , N J , Toga , A W , Visser , P J , Wade-Martins , R , Wilkinson , T , Williams , J , Wong , A & Gallacher , J E J 2020 , ' The Dementias Platform UK (DPUK) Data Portal ' , European Journal of Epidemiology , vol. 35 , no. 6 , pp. 601-611 . https://doi.org/10.1007/s10654-020-00633-4
The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
In: Gao , Y , Wang , T , Yu , X , Ferrari , R , Hernandez , D G , Nalls , M A , Rohrer , J D , Ramasamy , A , Kwok , J B J , Dobson-Stone , C , Brooks , W S , Schofield , P R , Halliday , G M , Hodges , J R , Piguet , O , Bartley , L , Thompson , E , Haan , E , Hernández , I , Ruiz , A , Boada , M , Borroni , B , Padovani , A , Cruchaga , C , Cairns , N J , Benussi , L , Binetti , G , Ghidoni , R , Forloni , G , Albani , D , Galimberti , D , Fenoglio , C , Serpente , M , Scarpini , E , Clarimón , J , Lleó , A , Blesa , R , Waldö , M L , Nilsson , K , Nilsson , C , Mackenzie , I R A , Hsiung , G Y R , Mann , D M A , Grafman , J , Morris , C M , Attems , J , Griffiths , T D , McKeith , I G , Thomas , A J , Pietrini , P , Huey , E D , Wassermann , E M , Baborie , A , Jaros , E , Tierney , M C , Pastor , P , Razquin , C , Ortega-Cubero , S , Alonso , E , Perneczky , R , Diehl-Schmid , J , Alexopoulos , P , Kurz , A , Rainero , I , Rubino , E , Pinessi , L , Rogaeva , E , George-Hyslop , P S , Rossi , G , Tagliavini , F , Giaccone , G , Rowe , J B , Schlachetzki , J C M , Uphill , J , Collinge , J , Mead , S , Danek , A , Van Deerlin , V M , Grossman , M , Trojanowski , J Q , van der Zee , J , Cruts , M , Van Broeckhoven , C , Cappa , S F , Leber , I , Hannequin , D , Golfier , V , Vercelletto , M , Brice , A , Nacmias , B , Sorbi , S , Bagnoli , S , Piaceri , I , Nielsen , J E , Hjermind , L E , Riemenschneider , M , Mayhaus , M , Ibach , B , Gasparoni , G , Pichler , S , Gu , W , Rossor , M N , Fox , N C , Warren , J D , Spillantini , M G , Morris , H R , Rizzu , P , Heutink , P , Snowden , J S , Rollinson , S , Richardson , A , Gerhard , A , Bruni , A C , Maletta , R , Frangipane , F , Cupidi , C , Bernardi , L , Anfossi , M , Gallo , M , Conidi , M E , Smirne , N , Rademakers , R , Baker , M , Dickson , D W , Graff-Radford , N R , Petersen , R C , Knopman , D , Josephs , K A , Boeve , B F , Parisi , J E , Seeley , W W , Miller , B L , Karydas , A M , Rosen , H , van Swieten , J C , Dopper , E G P , Seelaar , H , Pijnenburg , Y A L , Scheltens , P , Logroscino , G , Capozzo , R , Novelli , V , Puca , A A , Franceschi , M , Postiglione , A , Milan , G , Sorrentino , P , Kristiansen , M , Chiang , H H , Graff , C , Pasquier , F , Rollin , A , Deramecourt , V , Lebouvier , T , Kapogiannis , D , Ferrucci , L , Pickering-Brown , S , Singleton , A B , Hardy , J , Momeni , P , Zhao , H , Zeng , P & International FTD-Genomics Consortium (IFGC) 2020 , ' Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis ' , Scientific Reports , vol. 10 , no. 1 , 12184 . https://doi.org/10.1038/s41598-020-68848-9
We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.