JPND call 2014:  “ Working Groups to Inform Cohort Studies in Neurodegenerative Disease Research


Increasing the impact of longitudinal population studies for neurodegenerative disease research

The use of population studies offers a significant opportunity for research into factors affecting risk and progression of neurodegenerative disease, an opportunity that is greater than ever given the emergence of new molecular and digital technologies. However, to fully realise this potential there is a need to harmonise approaches and encourage collaboration and data sharing. In response to this, JPND commissioned ten groups of experts through a peer reviewed call for proposals to address methodological challenges preventing current population- and disease-based longitudinal cohorts being fully used for ND research.  A brief description of the valuable reports and recommendations provided by each group is provided below.

Philippe Amouyel, the Chair of JPND comments:

JPND recognises that longitudinal cohort studies are a rich but under-used resource. This is why we designed a rapid-action call to ask leading international experts to put their heads together to help exploit this opportunity and make population studies more accessible to a wider range of researchers. The guidelines that have been provided through this extensive body of work provide an important resource for the scientific community, which will help researchers increase collaborative activity and make productive use of longitudinal cohort studies. 


HD-READy: High Dimensional research in Alzheimer’s Disease

Slide3Coordinator: Professor M.Afran Ikram, Erasmus Medical Centre, Rotterdam, Netherlands


The report focuses on how to combine measurement of genetics and imaging, both important technologies in ND research, yet mostly studied in isolation. Until recently both fields have tended to use hypothesis-free approaches (GWAS, candidate gene approaches, measurement of voxels). Scientific advances have made more sophisticated technologies and focused (‘high dimensional’) approaches feasible, however these require new analytical methodology and infrastructure. The group recommends ways to decipher ultra-high dimensional ‘omics’ data with new analytical methodology, providing advice on the best approaches and recommending a new set of four  ‘HD-READY’ core principles to follow – around setting, speed, sharing and statistics.


Harmonization and innovation of cognitive behavioural and functional assessment in neurodegenerative dementias

Coordinator: Dr Alberto Costa, IRCDCS Fondazione Santa Lucia, Rome, Italy


This expert group makes recommendations for harmonisation when developing tests for neuropsychological assessment of people with neurodegenerative conditions where cognition is affected. The report advises on the main aspects to address in the tests, and highlights the importance of ensuring validity and reliability. Specific guidance is provided on how to design studies that can provide empirical evidence for selecting between methods for diagnosis and monitoring of ND.  Emphasis is also placed on the need to improve knowledge about the sensitivity, specificity and predictive value of the currently used tools.


NETCALS (Network of Cohort Assessment in ALS) – A community-led expert group for population-based cohorts of ALS patients

Coordinator: Professor Leonard van den Berg, University Medical Centre Utrecht, Utrecht, Netherlands


The NETCALS expert group recognises that ALS is not a single disease and that different sub-groups of patients exist. The report proposes pan-European ‘best practice’ guidelines and a methodological framework for data sharing/ handling, cognitive/ functional outcome measures, standards for neuro-imaging/neurophysiology and clinical data linkage in population-based cohorts of ALS patients and pre-symptomatic gene carriers.


21st Century EURODEM– addressing the need for contemporary and representative population studies in dementia

Coordinator: Professor Carol Brayne, University of Cambridge, Cambridge, UK


This expert group focuses on how existing population based studies can be aligned to provide better descriptive data for ND disorders in contemporary older Europeans, with the overarching goal of dementias prevention through the study of clinical and biological risk factors.  A full epidemiological picture is needed to model and predict future clinical economic and social needs and to design public health interventions.

The expert group’s guidelines cover how population representation studies should be assessed, planned and integrated, including advice on the expertise needed within the multidisciplinary team. Guidance is tailored for funders, policy makers, journal editors and reviewers, cohort stewards, cohort investigators, other dementia researchers, charities and members of the public. A website has been established where an overview of European cohort studies and a synthesis of comparative European studies are available, and a suite of further papers will follow.


Multi-centre cohort studies in Lewy-Body Dementia: Challenges in harmonizing different clinical and biomarker protocols

Coordinator: Professor Dag Aarsland, Stavanger University Hospital, Stavanger, Norway


This expert group focuses on Lewy body dementia (DLB) for which few longitudinal studies exist, which represents a significant gap in the resource available to ND researchers.    Where studies do exist, these are on a single site with fewer than 100 patients, and currently there are no multicentre studies.

Very little is known about the pre-dementia, pro-dromal phases of DLB yet this knowledge is crucial for both clinical management and research, including clinical diagnostic and biomarker criteria.  Recommendations are made to facilitate new longitudinal studies and on how best to combine data from different existing cohorts with different protocols. The clinical and research records from more than 1100 DLB patients from over 20 European centres have been collected and systematized. Finally, work has begun to develop DLB criteria based on retrospective analyses of data from previous existing cohorts and with a view to establishing provisional prodromal criteria to be tested in a new cohort, should this be established.


Developing a methodological framework for trials in presymptomatic neurodegenerative disease – the Presymptomatic Neurodegeneration Initiative (PreNI)

Coordinator: Dr Jonathan Rohrer, University College London, London, UK


The expert group includes experts across a range of presymptomatic ND including Alzheimer’s disease, frontotemporal dementia, Huntington’s disease, Parkinson’s disease, prion disease, motor neuron disease and the spinocerebellar ataxias.  Recommendations derived from a questionnaire and the workshops cover the planning for future trials, including the use of adaptive or run-in trial designs, early assessment of feasibility of trial design, validation and harmonization of biomarkers, and appropriate consideration of ethical issues at an early stage in conjunction with trial design.


BioLoC-PD: Harmonization of biomarker assessment in longitudinal cohort studies in Parkinson’s disease

Coordinator: Professor Daniela Berg, Hertie-Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, Germany


The expert group carried out a questionnaire survey of the design, markers and clinical assessments undertaken in ongoing longitudinal studies represented by its membership, with goals of defining consistent common markers for prediction and progression of PD and/or an assessment test battery. Also conducted were two systematic literature searches on current assessments and markers in the prodromal and clinical phases of PD.

Reasons were identified for the substantial variability found in the choice of evaluation method in the studies surveyed, leading to consensus on the functions and domains that would be most valuably assessed.  Based on these findings, the expert group proposes a three-level modular assessment battery to be implemented in new and ongoing longitudinal cohort studies for PD.  This contains a basic module for use with all participants across abroad range of different study types, including registers, and a minimum module to be applied to all individuals participating in at-risk prodromal and clinical longitudinal studies of PD. Finally an optimal extension module is proposed which may be used to evaluate parameters in study participants in more detail.


Dementia Outcome Measures: charting new territory

Coordinator: Professor Gail Mountain, University of Sheffield, Sheffield, UK


The report is for researchers across Europe engaged in psychosocial research in dementia care. It highlights how social health affects how people with ND adapt to, and self-manage their condition.

Early intervention is noted to be a relatively new area for service delivery and research evidence to support such interventions remains patchy, with over reliance on proxy measures for recording quality of life. The expert group makes recommendations on psychosocial measures for a range of dementias with an emphasis on direct reporting. The recommendation takes into account the need for involvement of clinicians, identifying measures that as far as possible are cost neutral and can routinely be applied in practice.


Body fluid biobanking of longitudinal cohorts in neurodegenerative diseases

Coordinator: Dr Charlotte Teunissen, VU University Medical Centre, Amsterdam, Netherlands


This expert group has developed guidelines and tools to facilitate the exchange of biological material between international cohorts of people with ND, which are to be made available through the International Society for Biological and Environmental Repositories (ISBER) Forum. These cover aspects such as stability testing of biomaterials such as blood and CSF and will be of particular use for groups studying novel biomarkers. A specific datawarehouse framework for biobanked biospecimens has been developed, known as the REDCap Biobanking tool, which will enable researchers to obtain and share information across sites about accessible bio samples.


Realising the potential of cohort studies to determine the vascular contribution to neurodegeneration

Coordinator: Professor Joanna Wardlaw, University of Edinburgh, Edinburgh, UK


Vascular disease is a dynamic and far-reaching process. The report focuses on the contribution of vascular comorbidities to ND, looking across hospital based cohorts, population cohorts and clinical trials across the globe.  The expert group uncovered a high level of new information from existing studies that overlapped very little with previous data collection. This suggests that the value of mining such data is very high.

The group concludes that vascular risk factors, disease burden and outcomes should be routinely evaluated in ND studies. Core sets of standard approaches are needed so that studies can be compared.  A series of specific recommendations are made, covering the integration of approaches, assessment of vascular risk factors in ND studies, performing cognitive assessments in vascular disease studies (to include executive function and processing speed in addition to memory function) and assessing gait as an indicator that there are early problems with vascular function. Other recommendations include collecting post mortem brain tissue from the regions beyond the hippocampus that are commonly affected by vascular disease.