The objectives of this paper are the analysis of the accident risk of drivers brain pathologies (Mild Cognitive Impairment, Alzheimer’s disease, and Parkinson’s disease), and the investigation of the impact of driver distraction on the accident risk of patients with brain pathologies, through a driving simulator experiment. The three groups of patients are compared to a healthy group of similar demographics, with no brain pathology. In particular, 125 drivers of more than 55 years old (34 “controls” and 91 “patients”) went through a large driving simulator experimental process, in which incidents were scheduled to occur. They drove in rural and urban areas, in low and high traffic volumes and in three distraction conditions (undistracted driving, conversation with a passenger and conversation through a mobile phone). The statistical analyses indicated several interesting findings; brain pathologies affect significantly accident risk and distraction affects more the groups of patients than the control one.