APPLICATION OF SYSTEMS MEDICINE TO ALZHEIMER'S DISEASE AND DEMENTIA RESEARCH: A SYSTEMATIC REVIEW

Systems medicine offers a novel paradigm that is well established in the study of complex chronic diseases that arise as the result of multiple interacting factors such as cancer and diabetes. Systems medicine models may help to account for the dynamic interactions between biological, clinical and environmental factors in Alzheimer's disease (AD) and dementia. Our aim was to examine the extent to which systems medicine has been applied to dementia research. We conducted a systematic review using EMBASE, Medline and PsycInfo from inception to January 2014 plus backward and forward citation searches of included publications following a pre-defined protocol (see Figure). Experts in the field were contacted to identify any additional relevant publications. We searched for publications applying a computational or mathematical model of AD or dementia and integrating dynamically interacting factors on multiple levels (biological, clinical and/or environmental). No date or language restrictions were used. Two reviewers independently screened titles and abstracts, and conducted full text reviews. Discrepancies were resolved by discussion with involvement of two additional reviewers. We selected 24 studies for full-text review. Two studies met all inclusion criteria and provide useful examples to illustrate the potential of the systems medicine paradigm. The first study incorporated a multifactorial computational model of AD pathogenesis, and was subsequently extended in the second study to incorporate the hypothesized role of estrogen in amyloid-beta regulation. They demonstrated that treatments directed at multiple targets may be more effective than single-target therapies, and make several experimentally testable predictions. These models took into account the dynamic interactions between biological and clinical factors, although the number of clinical factors was highly limited.