Biomarkers in preclinical Alzheimer's disease

With the recent advances in the treatment of Alzheimer's disease (AD) over the last decade, the focus has increasingly shifted to accurate detection of the earliest phase of illness. The intermediate state between normal aging and established AD is commonly known as mild cognitive impairment (MCI). Not all patients with MCI progress to AD and hence there is a need to reliably predict which patients with MCI will progress. The current inability of clinical criteria to accurately identify this at-risk group is fuelling the emerging interest in biomarkers to potentially supplement or replace clinical approaches. Biomarkers have the potential to clearly reflect the progressive deterioration that is present even in the earliest stages of AD--a useful feature for demonstrating the effectiveness or otherwise of a particular dementia drug. This paper will review the evidence regarding the use of cerebrospinal fluid, neuroimaging and blood biomarkers, as well as combination biomarkers, from the two standpoints of predicting MCI conversion to AD and monitoring disease progression at the MCI stage, so as to recommend which biomarkers can reasonably be included in early dementia trials, and how they can best be used.