Driving is a complex task that requires the ability to receive sensory information, process the information, and to make proper, timely judgments and responses. Older drivers or drivers suffering brain pathologies may have deficits in their driving ability (motor, visual, cognitive or perceptual) and these deficits may lead to reduced driver fitness and increased accident probability. These particularities of impaired driver’s behaviour and safety characteristics make the assessment of their driving ability a very challenging task especially regarding driver distraction. Driver distraction is estimated to be an important cause of vehicle accidents. Especially in the elderly and people with brain pathologies, because of the degradation of cerebral function, they may be particularly vulnerable to the effects of distraction; however, relatively few studies have examined the effect of cerebral diseases on distracted driving behaviour. The objective of this research is the analysis of two basic driving behaviour and safety parameters – reaction time and accident probability – of drivers with cognitive impairments due to various brain pathologies, in combination with invehicle distraction, using a driving simulator. An interdisciplinary research team of civil engineers, neurologists and psychologists is carrying out an experiment with three assessments for healthy and impaired drivers: a medical/neurological assessment, a neuropsychological assessment and a driving simulator task. The driving scenario examined concerns driving in rural area, with and without in-vehicle distraction (conversation with passenger and mobile phone use). The brain pathologies examined include early Alzheimer’s disease (AD), early Parkinson’s disease (PD), and Mild Cognitive Impairment (MCI). 140 participants (out of which 109 have some brain pathology) have completed the experiment. A statistical analysis was carried out by means of mixed generalized linear modelling (mixed GLM) and the results suggest that there are significant differences in the driving performance and safety of healthy drivers and drivers with cognitive impairments. Impaired drivers appear to react significantly slower at unexpected incidents than the healthy ones and are more likely to be involved in an accident. More specifically, AD and PD drivers seem to have the longest reaction times among the examined group. The mobile phone use seems to have a statistically significant negative effect on both reaction time and accident probability, especially in the AD participants. Finally, effects of conversation with passengers are less pronounced, although several differences in driving behaviour and safety of impaired drivers are identifiable.