Population-level pharmacogenomics for precision drug development in dementia

Introduction: There is an alarming lack of therapeutic options for dementia (Alzheimer's disease, vascular/mixed dementia). Despite the enormous effort made by scientists, industry and society, no medication has been approved for the treatment of dementia in almost two decades. In contrast, the affected population is a great consumer of pharmaceutical resources for the management of age-related and dementia-associated disorders, with a high risk of suffering adverse drug reactions which multiply the cost of the disease and aggravate its clinical course. The implementation of pharmacogenomic procedures may help to accelerate drug development and optimize the use of polypharmacy regimes. Areas covered: The areas covered include the following: determinants of pharmacological and pharmacogenomic outcomes (pathogenic, mechanistic, metabolic, transporter, pleiotropic genes), drug development, pharmacogenomics of dementia (anti-dementia drugs, treatment of cardio-cerebro-vascular risk factors, psychotropic drugs), pharmacoepigenomics, and novel drug targets. Expert commentary: Therapeutic strategies in dementia need a profound revision, novel drug targets should be urgently identified, and research programs demand a consequent reorientation. Precision medicine can be of help in this endeavor by introducing pharmacogenomic tools and satellite technologies into drug development and into safer disease management. Large-scale population studies and educational programs are necessary; and the practical application of personalized treatments should be simplified with digital devices.