Monoamine-Oxidase type B- Inhibitors and Cognitive Functions in Parkinson's Disease: Beyond the Primary Mechanism of Action.

Symptoms of cognitive impairment are rather common since the early stage of Parkinson's disease (PD), aggravate with disease progression and may lead to dementia in a significant proportion of cases. Worsening of cognitive symptoms in PD patients depends on the progression of subcortical dopaminergic damage as well as the involvement of other brain neurotransmitter systems in cortical and subcortical regions. Beyond the negative impact on disability and quality of life, the presence and severity of cognitive symptoms may limit adjustments of dopamine replacement therapy along disease course. This review focuses on the consequences of the administration of monoamine-oxidase type B-inhibitors (MAOB-I) on cognition in PD patients. Two drugs (selegiline and rasagiline) are available for treatment of motor symptoms of PD as monotherapy or in combination with L-DOPA or dopamine agonists in stable and fluctuating patients, a further drug (safinamide) is usable in fluctuating subjects solely. The results of available studies indicate differential effects according to disease stage and drug features. In early, non-fluctuating patients, selegiline and rasagiline ameliorated prefrontal executive functions, similarly to other dopaminergic drugs. Benefit on some executive functions was maintained in more advanced, fluctuating, patients, despite the tendency of worsening of prefrontal inhibitory control activity. Interestingly, high-dose safinamide improved inhibitory control in fluctuating patients. The benefit of high-dose safinamide on prefrontal inhibitory control mechanisms may stem from its dual mechanism of action, allowing reduction of excessive glutamatergic transmission, in turn secondary to increased cortical dopaminergic input.