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.
Alzheimer's disease is the most frequent cause of dementia in people 60 years and older. Epidemiological data as well as secondary data from German health insurances suggest an exponential increase of the prevalence of Alzheimer's disease and dementia after age 60. Prevalence are below 2% in age cohorts below 65 years, reach 5% at age 75 years and about 35% at age 90 years and older (Ferri et al., 2005 and Ziegler and Doblhammer, 2009). The increasing proportion of elderly in Germany and the predicted increase of life expectancy will lead to an increase of the number of demented people in Germany from 1.4 Million in 2010 to almost 3 Million in 2050 (Ziegler and Doblhammer, 2009).
Although these numbers illustrate the need for early diagnosis and treatment of dementia, it has been estimated that at most 50% of people with dementia receive a diagnosis in the primary care system (Stoppe et al., 1994 and Belmin et al., 2012). However, early clinical diagnosis is required to provide early medical treatment, including symptomatic anti-dementive medication (Birks, 2006), and systematic medication review (Jahns et al., 2012) to reduce the load of anticholinergic drugs. Medical treatment has been shown to be most efficient and cost effective if applied in early stages of dementia (Neumann et al., 1999, Teipel et al., 2007a, Teipel et al., 2007b and Teipel et al., 2007c). In addition, early diagnosis provides the chance for the patient and the family to make informed decisions and provides the opportunity to support and train the caregivers. Early care-giver based interventions are key elements for successful patient management to amend the course of disease, prevent behavioral symptoms and delay institutionalization (Olazaran et al., 2010). Already to date an early clinical diagnosis can be reached by using established standard procedures as proposed by national and international guidelines (NICE, 2006, DGPPN and DGN, 2010 and Hort et al., 2010). These procedures include a detailed clinical history and history by proxy, neuropsychological testing, a basic neurological examination and laboratory testing as well as structural imaging using CT or MRI to exclude other causes of dementia. Diagnosis in atypical cases and very early stages can further be supported by the use of neurodestruction markers in the CSF and cortical metabolic changes in FDG-PET.
