Application of Genetics in the Elderly: Development, Integration, Analyses - AGE-DIAmond: development of a model based on clinical and genetic determinants to predict clinical outcome

BACKGROUND: The burden of age-related chronic diseases, such as neurodegenerative disorders, led to an increasing interest in the risk factors for physical, psychological and functional decline. Frailty is a geriatric syndrome of decreased resistance to stressors and increased risk for adverse health outcomes that can be defined based on a multidimensional approach, such as the Multidimensional Prognostic Index (MPI). To date there is no available instrument to predict the clinical outcomes in the elderly that comprises also constitutional, biological and genetic factors. AIMS: The goal of this work was to design a real-world clinical protocol aimed to develop a predictive multidimensional model based on clinical, biological and genetic data, including biomarkers associated with frailty, ageing and cognitive decline. METHODS: The project team surveyed and critically appraised the current clinical procedures and the recommended protocols (including geriatric assessment, neuropsychological assessment and genetic counselling). The study design and the clinical protocol were revised until consensus was reached. RESULTS: A cross-sectional study was designed. All consecutive patients referred to the geriatrics unit for cognitive decline and/or frailty syndrome are eligible. The primary outcome measure is MPI. Secondary outcomes will include the longitudinal change of MPI, cognitive decline, mortality, hospitalization, pharmacological and non-pharmacological treatments response. Clinical assessment will be provided by a multidisciplinary team and will include geriatric clinical evaluation, neuropsychological examination and genetic counselling. Patients will be asked to fill a questionnaire for family history collection. A blood sample will be collected and stored for the biological and genetic investigations. For each patient, at least one follow-up visit will be performed. The study protocol was approved by the Regional Ethics Committee. Patients enrolment is expected to start in June 2017. CONCLUSIONS: The AGE-DIAmond study is envisaged to develop in a real-world setting a model which will validly predict clinical outcome in ageing individuals. Once an accurate and robust model is established, personalised preventive and therapeutic procedures can be successfully accomplished. The availability of valid biomarkers and of a robust predictive model may influence the design of clinical trials for innovative treatments. No conflict of interest declared. The work was partially granted by the University of Genova (Fondi Ricerca Ateneo 2015) to EDM.