Vascular contributions to cognitive impairment and dementia: Research consortia that focus on etiology and treatable targets to lessen the burden of dementia worldwide

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Abstract

The research into vascular contributions to cognitive impairment and dementia (VCID) aims to understand the importance of cerebrovascular biology in cognitive decline. Prevention and treatment of VCID is poised to have major impact on dementia-related disease burden and is thus a critical emerging objective in dementia research. This article presents VCID consortia focused on multidisciplinary approaches to identify key pathologic targets and develop diagnostic tools with the goal of bridging the divide between basic research and clinical trials. Members of these multi-institute, multidisciplinary consortia provide a prospective on the history and emerging science of VCID and how VCID consortia can address some of the more complex questions in VCID and drive the field forward. These consortia, and others like them, are uniquely suited to tackle some of the most difficult obstacles in translating research to the clinic.

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Most cited references 13

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Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.

G C Román, T K Tatemichi, T Erkinjuntti … (1993)

Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.

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Understanding the role of the perivascular space in cerebral small vessel disease.

Rosalind Brown, Helene Benveniste, Sandra Black … (2018)

Small vessel diseases (SVDs) are a group of disorders that result from pathological alteration of the small blood vessels in the brain, including the small arteries, capillaries and veins. Of the 35-36 million people that are estimated to suffer from dementia worldwide, up to 65% have an SVD component. Furthermore, SVD causes 20-25% of strokes, worsens outcome after stroke and is a leading cause of disability, cognitive impairment and poor mobility. Yet the underlying cause(s) of SVD are not fully understood. Magnetic resonance imaging has confirmed enlarged perivascular spaces (PVS) as a hallmark feature of SVD. In healthy tissue, these spaces are proposed to form part of a complex brain fluid drainage system which supports interstitial fluid exchange and may also facilitate clearance of waste products from the brain. The pathophysiological signature of PVS and what this infers about their function and interaction with cerebral microcirculation, plus subsequent downstream effects on lesion development in the brain has not been established. Here we discuss the potential of enlarged PVS to be a unique biomarker for SVD and related brain disorders with a vascular component. We propose that widening of PVS suggests presence of peri-vascular cell debris and other waste products that form part of a vicious cycle involving impaired cerebrovascular reactivity, blood-brain barrier dysfunction, perivascular inflammation and ultimately impaired clearance of waste proteins from the interstitial fluid space, leading to accumulation of toxins, hypoxia, and tissue damage. Here, we outline current knowledge, questions and hypotheses regarding understanding the brain fluid dynamics underpinning dementia and stroke through the common denominator of SVD.

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Vascular risk factors and dementia: how to move forward?

Christophe Tzourio, Anand Viswanathan, Walter A Rocca (2009)

In recent years, accumulating evidence has suggested that vascular risk factors contribute to Alzheimer disease (AD). Vascular dementia had been traditionally considered secondary to stroke and vascular disease. It has been traditionally distinguished from AD, considered to be a purely neurodegenerative form of dementia. However, in light of this more recent literature, it appears that there is a spectrum: ranging from patients with pure vascular dementia to patients with pure AD and including a large majority of patients with contributions from both Alzheimer and vascular pathologies. In this article, we discuss the impact of vascular risk factors on AD and its consequences at the individual level and at the population level by highlighting the concept of attributable risk. We then discuss the key questions and next steps involved in designing a therapeutic trial to control vascular risk factors for the prevention of dementia.

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Author and article information

Contributors

Jordan T. Gladman

Journal

Journal ID (nlm-ta): Alzheimers Dement (N Y)

Journal ID (iso-abbrev): Alzheimers Dement (N Y)

Title: Alzheimer's & Dementia : Translational Research & Clinical Interventions

Publisher: Elsevier

ISSN (Electronic): 2352-8737

Publication date PMC-release: 19 November 2019

Publication date Collection: 2019

Publication date (Electronic): 19 November 2019

Volume: 5

Pages: 789-796

Affiliations

[a ]Department of Neuroscience, National Institutes of Neurological Disorders and Stroke, Bethesda, MD, USA

[b ]University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, Bordeaux, France

[c ]Department of Neurology, University Hospital of Bordeaux, Bordeaux, France

[d ]Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-Universität LMU, Munich, Germany

[e ]German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany

[f ]Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

[g ]Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

[h ]Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia

[i ]Centre for Clinical Brain Sciences, UK Dementia Research Institute at the University of Edinburgh, Chancellor's Building, Little France, Edinburgh

[j ]Department of Neurology, G03.232, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands

Author notes

[∗ ]Corresponding author. Tel.: +1 3014965680; Fax: 1 3014022060. jordan.gladman@ 123456nih.gov

Article

Publisher ID: S2352-8737(19)30078-2

DOI: 10.1016/j.trci.2019.09.017

PMC ID: 6944727

SO-VID: b7b9ee75-e4d0-42ec-a025-b472306c8331

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Vascular contributions to cognitive impairment and dementia: Research consortia that focus on etiology and treatable targets to lessen the burden of dementia worldwide

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Vascular Biology

Most cited references 13

Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.

Understanding the role of the perivascular space in cerebral small vessel disease.

Vascular risk factors and dementia: how to move forward?

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