METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: An initiative of the Joint Programme for Neurodegenerative Disease Research.

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically "silent" cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.The following funders supported the work. Joint Programme for Neurodegenerative Disease (JPND) Research, specifically the UK Medical Research Council, the Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) and the Canadian Institutes of Health Research (CIHR). The Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) through the Pools Engagement in Europe (PEER) funding from the Scottish Funding Council. The Therese Pei Fong Chow Research Centre for Prevention of Dementia (in memory of Donald H K Chow). We thank the Siemens Foundation, Munich, Germany for providing the workshop venue and catering. F-EdeL acknowledges VIDI Innovation Grant from ZonMW ref 016.126.351. PMM acknowledges generous support from the Edmond J Safra Foundation and Lily Safra and the Imperial College Health Trust BRC. PMWB is Stroke Association Professor of Stroke Medicine. CdeC acknowledges support from Centre Grant NIH P30 AG 010129.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.jalz.2016.06.00

METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: An initiative of the Joint Programme for Neurodegenerative Disease Research

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention

Bipolar Patients with Vascular Risk Display a Steeper Age-Related Negative Slope in Inhibitory Performance but Not Processing Speed: A Preliminary Study

OBJECTIVE: Bipolar disorder (BD) is associated with cognitive deficits, yet little is known about associations between cognition, vascular risk (VR) and age in this population. This study investigated whether BD patients with VR demonstrate stronger apparent age-related decline in inhibitory performance and processing speed (PS). METHODS: A full medical history was obtained for 34 euthymic BD and 41 healthy comparison (HC) individuals. The Delis-Kaplan Executive Functions Color Word Interference Subtests was administered to all participants to assess for inhibitory performance (condition 3) and PS (condition 1 and 2). VR positive (VRPos) and VR negative (VRNeg) groups were created based on the presence of one or more VR factors. RESULTS: VRPos-BD participants demonstrated significantly worse inhibitory performance with older age, while age and inhibition were not significantly related in the VRPOS-HC group or in those who were VRNeg. The same was not true for PS. CONCLUSION: BD patients with VR may also be at risk for greater decline in inhibitory performance, but not PS, with age. Longitudinal studies are needed to further investigate the contributions of VR to cognitive decline among older BD patients

Small vessels, dementia and chronic diseases – molecular mechanisms and pathophysiology

Cerebral small vessel disease (SVD) is a major contributor to stroke, cognitive impairment and dementia with limited therapeutic interventions. There is a critical need to provide mechanistic insight and improve translation between pre-clinical research and the clinic. A 2-day workshop was held which brought together experts from several disciplines in cerebrovascular disease, dementia and cardiovascular biology, to highlight current advances in these fields, explore synergies and scope for development. These proceedings provide a summary of key talks at the workshop with a particular focus on animal models of cerebral vascular disease and dementia, mechanisms and approaches to improve translation. The outcomes of discussion groups on related themes to identify the gaps in knowledge and requirements to advance knowledge are summarized