The objective of the present inter-disciplinary PhD dissertation is the analysis of traffic and safety behaviour of drivers with neurological diseases affecting cognitive functions. More specifically, the impact of brain pathologies on reaction time, accident probability, driving errors, and driving performance is under investigation. The driving behaviour is examined in terms of both traffic and safety behaviour and the neurological diseases affecting cognitive functions concern Alzheimer’s disease (AD), Parkinson’s disease (PD), and Mild Cognitive Impairment (MCI). A large-scale driving simulator experiment was carried out, comprising a medical/neurological and neuropsychological assessment of 225 drivers, and a set of driving tasks for different scenarios. An innovative statistical analysis methodology has been developed and implemented, based on Regression Models, Principal Component Analysis and Structural Equation Models. Results indicated that the impact of neurological diseases affecting cognitive functions is significantly detrimental on traffic and safety behaviour. The AD group had the worse driving performance profile among the examined brain pathologies and finally, the negative impact of the mobile phone use on driving performance was much more pronounced on drivers with neurological diseases affecting cognitive functions than on healthy controls of similar demographics.