Imaging, subjective complaints, and MCI: 30 years before.

The neuropathological and cognitive changes preceding Alzheimer's disease (AD) appear to begin decades before disease symptoms make the clinical diagnosis obvious. Clinical trials have begun to focus on preventive treatments aimed to slow cognitive decline in people with only subjective memory complaints. However, it is not clear how many years before clinical diagnosis of Alzheimer's disease is possible to recognize early signs of neurodegeneration. We report evidence from the literature showing feasibility to diagnose AD at the stage of mild cognitive impairment (MCI) and also a few years before the MCI stage with imaging markers. However, we showed that neuroimaging brain changes evidenced decades before MCI are not early signs of neurodegeneration but expression of genetic risk states for AD or markers of inter-individual variability of cognitive performance due to genetic or environmental factors.