This is a study on the longitudinal evaluation of cognitive functions in multiple sclerosis (MS) patients and their quality of life (QoL). The study follow-up lasted for 3 years and the evaluation was performed every 9 months for four times altogether. We present data on the first and second session, when we evaluated the frontal component of cognitive functions, behavioural memory and quality of life. We administered the Luria Frontal Lobe Syndrome test (LFLS), the Rivermead Behavioural Memory Test (RBMT), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), SF-36 for QoL evaluation. The frontal component of cognitive functions and behavioural memory involvement is related to a worsening of QoL, in particular in the Physical Functioning and the Mental Health of SF-36.