Risk and resilience: A new perspective on Alzheimer's disease

Demographic and epidemiological studies predict an increasing number of people with Alzheimer's disease and dementia worldwide. Early diagnosis and intervention will help to attenuate the course of disease and lower its burden on patients, care-givers and the health care systems. Going even beyond early clinical diagnosis, new diagnostic research criteria define preclinical and predementia stages of Alzheimer's disease based on imaging and neurochemical biomarkers. Studying Alzheimer's disease in its preclinical stages gives researchers the chance to explore how brain function and structure mediates the effect of amyloid and other molecular lesions on cognitive performance and how this interaction is modulated by genetic and environmental risk and protective factors. This will have three major implications: (i) to design novel intervention studies that aim to strengthen protective factors and cognitive reserve, (ii) to provide an in vivo test system for the mode of action of potentially protective interventions, and (iii) to serve as a secondary endpoint for the effectiveness of interventions. This review summarizes key findings of the best established imaging markers of Alzheimer's disease, including markers of amyloid, metabolic and synaptic function, structural connectivity and brain atrophy. It outlines the present and future role of multimodal imaging in defining a preclinical stage of Alzheimer's disease and in the identification and evaluation of factors of risk and resilience of Alzheimer's disease.