No abstract

Background: Prior studies report that monoamine oxidases inhibitors (MAO-I) when used as an adjunct to levodopa ameliorate motor symptoms in Parkinson’s disease (PD), but this was not tested in relation to cognitive or psychiatric measures.Objective: Here, we tested the effects of MAO-I as an adjunct to levodopa, in comparison to levodopa or dopamine (DA) agonists alone, on various cognitive, affective and quality of life measures.Methods: We studied three groups of subjects: healthy controls, PD patients on combined levodopa and MAO-I, and PD patients on levodopa or DA agonists only.Results: We found that compared to monotherapy, combined MAO-I and levodopa seemed to improve cognition, including probabilistic learning, working memory and executive functions. There were no differences between the different medication regimes on deterministic learning, attention or memory recall. It was also found that MAO-I as an adjunct to levodopa improves affective measures such as depression, apathy, anxiety and quality of life. Interestingly, this enhancing effect of combined levodopa and MAO-I was more pronounced in PD patients with severe akinesia, compared to patients with severe tremor.Conclusion: Our data are in agreement with (a) the Continuous Dopaminergic Stimulation (CDS) theory which states that continuous stimulation of the basal ganglia enhances motor, psychiatric and cognitive functions in PD patients; and/or (b) findings that MAO-I increase the bioavailability of monoamines that have beneficial effects on motor and behavioral dysfunction in PD.

Damage to the hippocampal and frontostriatal systems can occur across the adult life span. As these 2systems are involved in learning processes, mild impairments of learning and generalization might be observed even in healthy aging. In this study, we examined both learning and generalization performance in 3 groups of older adults: young-older (ages 45–60), middle-older (ages 61–75), and oldest-older (ages 76–90).We used a simple computerized concurrent discrimination task in which the learning phase has demonstrated sensitivity to frontostriatal dysfunction, and the generalization phase to hippocampal damage. We found that age significantly affected initial learning performance, but generalization was spared in all but the oldest group, with some individuals still generalizing very well. This finding suggests that (a) learning abilities are affected in healthy aging (consistent with earlier reports of frontostriatal dysfunction in healthy aging) and (b) generalization deficit does not necessarily occur in early older age. We hypothesize that generalization deficits in some in the oldest group may be related to hippocampal pathology. Our data shed light on possible neural system dysfunction in healthy aging and Alzheimer disease.

Although hypothetical, our data may suggest that the hippocampus is a neural substrate underlying the occurrence of psychosis, sleep disturbance and cognitive impairment in PD patients.