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Can small-vessel disease-related cerebral abnormalities be used as a surrogate marker for vascular dementia trials?

  • F. Fazekas
  • S. Ropele
  • R. Schmidt
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 62)

Abstract

Clinical scales for measuring the effectiveness of disease modifying therapies in patients with vascular dementia are of limited sensitivity. Moreover, they cannot serve to directly probe the potential of a drug in slowing further progression of vascular damage. Assessment of morphologic babormalities that reflect ischemia-related cerebral tissue changes and have a bearing on cognitive function could serve to address both of these aspects and, if sensitive enough, could constitute an ideal surrogate for measuring progresssion of the disease. For drug licensing agencies a validated surrogate has to meet several requirements: First, the surrogate must predict the future clinical course. Second, the effect of treatment on the disease must be explained by the effect of the treatment on the surrogate; the treatment needs to affect clinical outcome by working through mechanisms related to the surrogate. Third, evidence must exist that treatments of various classes affect the surrogate in the same and predictable manner. Apart from these requirements, regulatory guidelines may also allow the use of even an unvalidated surrogate if it is considered reasonably likely to predict future clinical outcome or disease activity. Various morphologic measures, particularly those using conventional or more sophisticated MRI techniques have already shown a close correlation to neuropsychologic functions. If these associations can also be confinned in longitudinal studies and following specific treatments, morphologic markers will play a major role in future clinical trials of vascular dementia.

Keywords

Vascular Dementia White Matter Hyperintensities Vascular Cognitive Impairment High Cortical Function Poststroke Dementia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Wien 2002

Authors and Affiliations

  • F. Fazekas
    • 1
  • S. Ropele
    • 1
  • R. Schmidt
    • 1
  1. 1.Department of Neurology and MR CentreKarl Franzens UniversityGrazAustria

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