Affiliations: Department of Neurosciences, University of California,
San Diego, USA | Department of Radiology, University of California, San
Diego, USA | Division of Biostatistics and Bioinformatics,
University of California, San Diego, USA | Banner Alzheimer's Institute, Phoenix, AZ, USA
Note: [] Corresponding author: Adam S. Fleisher, MD, Banner Alzheimer's
Institute, 901 E Willetta Street, Phoenix, AZ 85383. Tel.: +1 602 239 6979;
Fax: +1 602 239 6499; E-mail: [email protected]
Abstract: Critical to development of new therapies for Alzheimer's disease
(AD) is the ability to detect clinical or pathological change over time.
Clinical outcome measures typically used in therapeutic trials have
unfortunately proven to be relatively variable and somewhat insensitive to
change in this slowly progressive disease. For this reason, development of
surrogate biomarkers that identify significant disease-associated brain changes
are necessary to expedite treatment development in AD. Since AD pathology is
present in the brain many years prior to clinical manifestation, ideally we
want to develop biomarkers of disease that identify abnormal brain structure or
function even prior to cognitive decline. Magnetic resonance imaging,
fluorodeoxyglucose positron emission tomography, new amyloid imaging
techniques, and spinal fluid markers of AD all have great potential to provide
surrogate endpoint measures for AD pathology. The Alzheimer's disease
neuroimaging initiative (ADNI) was developed for the distinct purpose of
evaluating surrogate biomarkers for drug development in AD. Recent evidence
from ADNI demonstrates that imaging may provide more sensitive, and earlier,
measures of disease progression than traditional clinical measures for powering
clinical drug trials in Alzheimer's disease. This review discusses recently
presented data from the ADNI dataset, and the importance of imaging in the
future of drug development in AD.
