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Treatment of Moderate to Severe Alzheimer's Disease: Rationale and Trial Design

  • Nathan Herrmann (a1)

Abstract

Moderate to severe Alzheimer's disease (AD) is characterized by increasing cognitive, functional, and behavioural dysfunction that results in increased caregiver burden and, eventually, complete dependence. Despite its significance as a societal health problem, there are few treatment trials of cognitive enhancers or disease modifying agents for this stage of illness. Studies suggest the cholinesterase inhibitors, especially donepezil, may provide benefit. Several studies provide support for the use of the NMDA receptor antagonist memantine as monotherapy or added to a cholinesterase inhibitor for moderate to severe AD. While there are no published guidelines for the treatment of moderate to severe AD, these studies do provide guidance for recommendations for study design and outcome measures. Such studies are urgently needed.

RÉSUMÉ:

La maladie d'Alzheimer de modérée à sévère est caractérisée par une dysfonction cognitive, fonctionnelle et comportementale progressive qui engendre un fardeau croissant pour les soignants et une dépendance complète éventuelle. En dépit de son importance comme problème de santé au niveau sociétal, il existe peu d'essais thérapeutiques portant sur des stimulateurs cognitifs ou des agents modificateurs de la maladie à ce stade de la maladie. Les études suggèrent que les inhibiteurs de la cholinestérase, spécialement le donépézil sont bénéfiques. Selon plusieurs études, l'utilisation de la mémantine, un antagoniste du récepteur NMDA, en monothérapie ou en association à un inhibiteur de la cholinestérase serait bénéfique dans la MA de modérée à sévère. Bien qu'il n'y ait pas de lignes directrices publiées concernant le traitement de la MA de modérée à sévère, ces études peuvent servir de guide pour formuler des recommandations sur le plan d'étude et les critères d'évaluation. Il est urgent de procéder à de telles études.

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Copyright

Corresponding author

Department of Psychiatry, Division of Geriatric Psychiatry, Faculty of Medicine, University of Toronto, Sunnybrook & Women's College Health Sciences Centre, Toronto, Ontario, M4N 3M5, Canada.

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