Imaging biomarkers and their role in dementia clinical trials.

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.