Quantitative magnetic resonance techniques as surrogate markers of Alzheimer's disease.

Recent advances in understanding the molecular biology of Alzheimer's disease (AD) offer the promise of useful therapeutic intervention in the foreseeable future. Hence, improved methods for early diagnosis and noninvasive surrogates of disease severity in AD have become more imperative. Various quantitative magnetic resonance (MR) techniques that measure the anatomic, biochemical, microstructural, functional, and blood-flow changes are being evaluated as possible surrogate measures of disease progression. Cross-sectional and longitudinal studies indicate that MR-based volume measurements are potential surrogates of disease progression in AD, starting from the preclinical stages. The validity of MR-based volumetry as a surrogate marker for therapeutic efficacy in AD remains to be tested in a positive disease-modifying drug trial. Recent development of amyloid imaging tracers for positron emission tomography has been a major breakthrough in the field of imaging markers for AD. Efforts to image plaques are also underway in MR imaging. As with indirect MR measures, these approaches of directly imaging the pathological substrate will need to undergo a validation process with longitudinal studies to prove their usefulness as surrogate markers in AD.