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Primary Prevention and Delay of Onset of AD/Dementia

Published online by Cambridge University Press:  02 December 2014

Howard H. Feldman  and
Claudia Jacova
Howard H. Feldman*
Affiliation:
The Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, B.C., Canada
Claudia Jacova
Affiliation:
The Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, B.C., Canada
*
Division of Neurology, UBC Hospital, S 192-2211 Wesbrook Mall, Vancouver, B.C., V6T 2B5, Canada.
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Abstract

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Prevention in Alzheimer's disease and other dementias (AD/dementia) is defined on the basis of clinical states and their expressed symptoms. Primary prevention refers to delaying the development of the full-blown state of clinically expressed disease in normal individuals. Current primary prevention research is driven by evidence of AD/dementia protective factors that have emerged from epidemiological studies. The first randomized controlled trials (RCTs) of primary AD/dementia prevention have been designed to test the efficacy and safety of NSAIDs, hormonal therapy, antihypertensive drugs and antioxidants. The experience of these trials has indicated safety concerns as a key issue and highlighted significant design challenges in this type of research. These trials have required large sample sizes and unsustainable costs. There should be consideration given in future trials to enriching study samples with risk factors to increase progression rates to AD/dementia. Innovative strategies will also be needed to recruit and retain subjects given the long follow-up periods, modest perceived benefit and the potential for the risk-benefit ratio to change during the trial. It is foreseeable that regulatory authorities will be presented with primary prevention RCTs for approval and labelling, and that criteria to evaluate such evidence still need to be developed.

Résumé:

RÉSUMÉ:

La prévention de la maladie d'Alzheimer (MA) et des autres démences (MA/démence) se définit sur des bases cliniques et symptomatiques. En prévention primaire, on cherche à retarder l'apparition de la maladie avérée au point de vue clinique chez des individus normaux. Actuellement, la recherche en prévention primaire est basée sur des données provenant d'études épidémiologiques sur les facteurs de protection contre la MA/démence. Les premiers essais contrôlés randomisés (ECRs) en prévention primaire sur la MA/démence ont été conçus pour évaluer l'efficacité et la sécurité d'AINSs, de traitements hormonaux, d'antihypertenseurs et d'antioxydants. L'expérience acquise au cours de ces études a soulevé des questions importantes concernant la sécurité et a fait ressortir des défis importants quant au plan de ce type de recherche. Ces essais nécessitent de très grands échantillons et entraînent des coûts prohibitifs. À l'avenir, on devrait considérer enrichir les groupes en incluant des sujets ayant des facteurs de risque afin d'augmenter le taux de progression à la MA/démence. Des stratégies novatrices seront également nécessaires pour recruter et maintenir la participation des sujets aux études étant donné le suivi à long terme, les bénéfices perçus comme étant modestes et le taux de risques/bénéfices qui peut changer pendant l'étude. Il est à prévoir que des ECRs en prévention primaire seront présentés aux organismes de régulation pour approbation et étiquetage du conditionnement des médicaments et que des critères d'évaluation des données ainsi générées devront être développés.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue S1 , March 2007 , pp. S84 - S89
Copyright
Copyright © The Canadian Journal of Neurological 2007

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