, Volume 2, Issue 2, pp 348–360

Neuroimaging biomarkers for clinical trials of disease-modifying therapies in Alzheimer’s disease



The pathophysiologic process leading to neurodegeneration in Alzheimer’s disease (AD) is thought to begin long before clinical symptoms develop. Existing therapeutics for AD improve symptoms, but increasing efforts are being directed toward the development of therapies to impede the pathologic progression of the disease. Although these medications must ultimately demonstrate efficacy in slowing clinical decline, there is a critical need for biomarkers that will indicate whether a candidate disease-modifying therapeutic agent is actually altering the underlying degenerative process. A number ofin vivo neuroimaging techniques, which can reliably and noninvasively assess aspects of neuroanatomy, chemistry, physiology, and pathology, hold promise as biomarkers. These neuroimaging measures appear to relate closely to neuropathological and clinical data, such as rate of cognitive decline and risk of future decline. As this work has matured, it has become clear that neuroimaging measures may serve a variety of potential roles in clinical trials of candidate neurotherapeutic agents for AD, depending in part on the question of interest and phase of drug development. In this article, we review data related to the range of neuroimaging biomarkers of Alzheimer’s disease and consider potential applications of these techniques to clinical trials, particularly with respect to the monitoring of disease progression in trials of disease-modifying therapies.

Key Words

Alzheimer’s disease mild cognitive impairment magnetic resonance imaging positron emission tomography single-photon emission tomography clinical drug trials biomarkers 


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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc 2005

Authors and Affiliations

  • Bradford C. Dickerson
    • 1
    • 2
    • 3
    • 4
  • Reisa A. Sperling
    • 1
    • 2
    • 3
  1. 1.Department of Neurology and the Athinoula A. Martinos Center for Biomedical ImagingMassachusetts General HospitalCharlestown
  2. 2.Memory Disorders Unit, Division of Cognitive and Behavioral Neurology, Department of NeurologyBrigham & Women’s HospitalBoston
  3. 3.Department of NeurologyHarvard Medical SchoolBoston
  4. 4.Gerontology Research UnitMassachusetts General HospitalCharlestown

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