Imaging-based measures of disease progression in clinical trials of disease-modifying drugs for Alzheimer disease.

The authors review and assess imaging-based strategies for measuring the rate of progression of Alzheimer disease (AD). Such techniques may be useful in addition to the behavioral instruments typically used in these studies and may be more sensitive to treatment-related change. MEDLINE searches obtained relevant published literature. Articles were reviewed with particular attention to assessments of rate of disease progression and the effects of investigational drugs. Authors studied a variety of techniques, including volumetric magnetic resonance imaging, functional MRI, fluorodeoxyglucose positron emission tomography, and several target-specific radiopharmaceuticals. In cross-sectional as well as small longitudinal trials, many of these show promise not only in diagnosis, but also as measures of disease progression. The effects of drugs that provide symptomatic relief on these measures have not been fully characterized. Even less is known about the effects of investigational drugs that may slow disease progression. Several neuroimaging techniques have been studied that could improve the ability of clinical trials to quantify the rate of progression of AD. Clinical trials of investigational drugs would benefit from more systematic validation of image-based outcome measures. Several choices of imaging techniques are available. An understanding of the relationship between a statistically significant effect size in an imaging marker and a clinically significant change in rate of disease progression will require additional studies.