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Therapeutic Issues in Vascular Dementia: Studies, Designs and Approaches

Published online by Cambridge University Press:  02 December 2014

Sandra E. Black*
Affiliation:
Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
*
Sunnybrook Health Sciences Centre, 2075 Bayview Ave.-A421, Toronto, Ontario, M4N 3M5, Canada.
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Abstract

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Vascular dementia (VaD) is a heterogeneous disorder resulting from various cerebrovascular diseases (CVD) causing cognitive impairment that reflects severity and location of damage. Epidemiological studies suggest VaD is the second commonest cause of dementia, but autopsy series report that pure VaD is infrequent, while combined CVD and Alzheimer's Disease(AD) is likely the commonest pathological-dementia correlate. Both diseases share vascular risk factors and benefit from their treatment. The most widely used diagnostic criteria for VaD are highly specific but not sensitive. Vascular Cognitive Impairment (VCI) is a dynamic, evolving concept that embraces VaD, Vascular Cognitive Impairment No Dementia (VCIND) and mixed AD and CVD. Clinical trials to date have focused on probable and possible VaD with beneficial effects evident for different drug classes, including cholinergic agents and NMDA agonists. Limitations have included use of cognitive tools suitable for AD that are insensitive to executive dysfunction. Disease heterogeneity has not been adequately controlled and subtypes require further study. Diagnostic VaD criteria now 13 years old need updating. More homogeneous subgroups need to be defined and therapeutically targeted to improve cognitive-behavioural outcomes including optimal control of vascular risk factors. More sensitive testing of executive function outlined in recent VCI Harmonization criteria and longer trial duration are needed to discern meaningful effects. Imaging criteria must be well-defined, with centralized review and standardized protocols. Serial scanning with quantification of tissue atrophy and lesion burden is becoming feasible, and cognitive interventions, including rehabilitation pharmacotherapy, with drugs strategically coupled to cognitive -behavioural treatments, hold promise and need further development.

Résumé:

RÉSUMÉ:

La démence vasculaire (DVa) est une entité hétérogène résultant de différentes maladies cérébrovasculaires (MCV) qui causent une atteinte cognitive reflétant la sévérité et la localisation des dommages. Les études épidémiologiques suggèrent que la DVa est la deuxième cause de démence, mais des études anatomopathologiques de matériel prélevé à l'autopsie démontrent que la MCV pure est rare et que l'association MCV et maladie d'Alzheimer (MA) est vraisemblablement le plus fréquent corrélat pathologie-démence. Les facteurs de risque vasculaires sont communs aux deux maladies et leur contrôle est bénéfique aux deux maladies. Les critères diagnostiques les plus utilisés pour la DVa sont très spécifiques mais ne sont pas sensibles. L'atteinte cognitive vasculaire (ACV) est un concept dynamique en évolution qui comprend la DVa, l'atteinte cognitive vasculaire sans démence (ACVSD) et la MA avec MCV. Jusqu'à maintenant, les essais cliniques ont ciblé la DVa probable et la DVa possible. Les bénéfices ont été évidents dans les essais portant sur différentes classes de médicaments, dont les agents cholinergiques et les agonistes de la NMDA. Une des limites de ces études est l'utilisation d'outils cognitifs appropriés à la MA qui sont insensibles à la dysfonction exécutive. On n'a pas suffisamment tenu compte de l'hétérogénéité de la maladie et on devra faire des études sur les sous-types de démence. Les critères diagnostiques de la DVa ont été établis il y a 13 ans et devraient être révisés. On doit définir des sous-groupes plus homogènes et cibler l'amélioration des résultats cognitifs et comportementaux ainsi que le contrôle optimal des facteurs de risque vasculaires. Les critères d'harmonisation de l'ACV établissent les grandes lignes de tests plus sensibles pour évaluer la fonction exécutive et des essais plus longs devront être faits pour faire ressortir les effets significatifs. Les critères d'imagerie devront être mieux définis, avec révision centrale et protocoles standardisés. L'imagerie en série avec quantification de l'atrophie tissulaire et du fardeau des lésions est maintenant possible et les interventions cognitives, dont la pharmacothérapie de réadaptation avec des médicaments ciblant stratégiquement la cognition et le comportement, sont prometteuses. On doit poursuivre leur développement.

Type
Original Articles
Copyright
Copyright © The Canadian Journal of Neurological 2007

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