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Imaging Biomarkers and their Role in Dementia Clinical Trials

Published online by Cambridge University Press:  02 December 2014

Howard Chertkow  and
Sandra Black
Howard Chertkow*
Affiliation:
Canada
Sandra Black
Affiliation:
Canada
*
Canada
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Abstract

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There are five potential major roles for neuroimaging with respect to dementia; 1) as a cognitive neuroscience research tool, 2) for prediction of which normal or slightly impaired individuals will develop dementia and over what time frame, 3) for early diagnosis of Alzheimer's disease (AD) in demented individuals, (sensitivity) and separation of AD from other forms of dementia (specificity), 4) for monitoring of disease progression, and 5) for monitoring response to therapies. Focusing on the last role, no single imaging approach is yet ideal, as all trade-off speed, cost, and accuracy. Functional imaging (SPECT and PET) is best suited to tracking symptomatic therapy response, and anatomic (MRI volumetric) imaging or amyloid PET are more suited to reflect dementia modulation studies. The potential for imaging with respect to pharmacological studies of dementia - to provide surrogate markers for drug studies, to improve diagnosis, to speed evaluation of outcomes, and to decrease sample sizes - is huge. At the present time, however, no single measure has sufficient proven reliability, replicability, or robustness, to replace clinical primary outcome measures.

Résumé:

RÉSUMÉ:

Il existe cinq rôles majeurs de la neuroimagerie dans l’évaluation de la démence : 1) comme outil de recherche en neuroscience cognitive; 2) pour prédire quels individus normaux ou présentant une légère atteinte cognitive développeront une démence et dans quel laps de temps; 3) pour poser un diagnostic précoce de maladie d’Alzheimer (MA) chez des individus déments (sensibilité) et pour distinguer la MA des autres démences (spécificité); 4) pour suivre la progression de la maladie et 5) pour évaluer la réponse au traitement. À ce propos, aucune approche d’imagerie ne s’est avérée idéale jusqu’à maintenant, parce que toutes font des compromis en ce qui concerne la rapidité, le coût et la précision. L’imagerie fonctionnelle (TEMP et TEP - SPECT and PET) est une meilleure approche pour suivre la réponse thérapeutique symptomatique et l’imagerie anatomique (IRM volumétrique) ou le TEP de la substance amyloïde conviennent mieux aux études de modulation de la démence. Le potentiel de l’imagerie dans les études pharmacologiques portant sur la démence est énorme : pour fournir des marqueurs de substitution pour l’étude de médicaments, pour améliorer le diagnostic, pour accélérer l’évaluation des résultats et pour diminuer la taille d’échantillon. Actuellement, aucune mesure ne s’est avérée suffisamment fiable, reproductible ou sûre pour remplacer les principales mesures d’impact clinique.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue S1 , March 2007 , pp. S77 - S83
Copyright
Copyright © The Canadian Journal of Neurological 2007

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