The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: A randomized, double‐blind, placebo‐controlled, multicenter study

Abstract

Cognitive impairment can occur at all stages of Parkinson's disease. Rasagiline is a selective monoamine oxidase type-B inhibitor that enhances central dopaminergic transmission. Dopamine is thought to be involved in certain cognitive processes such as working memory. We assessed the effects of rasagiline on cognitive deficits in cognitively impaired, nondemented patients with Parkinson's disease. This was a randomized, double-blind, placebo-controlled prospective study. Patients with Parkinson's disease receiving stable dopaminergic treatment were assigned to receive rasagiline 1 mg/day or placebo for 3 months. Patients were eligible if they had impairment in 2 of 4 cognitive domains (attention, executive functions, memory, visuospatial functions) in the screening neuropsychological tests, yet did not fulfill criteria for Parkinson's disease dementia. Fifty-five patients were randomized; 48 patients completed the study. Patients in the rasagiline group showed significant improvement in digit span-backward compared with the placebo group (P = .04), with trends favoring rasagiline in digit span total and digit-ordering tests. Verbal fluency total score showed a significant difference in favor of rasagiline (P = .038), with trends favoring rasagiline in semantic fluency test and Stroop spontaneous corrections. The composite cognitive domain Z scores revealed a significant difference in favor of rasagiline compared with placebo in the attentional Z score (P < .005). There were no significant differences between the 2 groups in the other cognitive tests or cognitive domain Z scores. The monoamine oxidase type-B inhibitor rasagiline may exert beneficial effects on certain aspects of attention and executive functions in nondemented patients with Parkinson's disease with cognitive impairment.

Effects of combined MAO-B inhibitors and levodopa vs. monotherapy in Parkinson’s disease

“…Further, in an 8-week study, it was found that selegiline did not have an effect on executive function using the Wisconsin Card Sorting Test (Dalrymple-Alford et al, 1995). Recently, Hanagasi et al (2011) found that compared to placebo, the MAO-B inhibitor rasagiline has a better effect on attention and executive function in nondemented PD patients. In this double blind placebo controlled multicenter trial of 48 non-demented patients with PD and cognitive impairment, significant improvement was noticed in the rasagiline group on scores of digit span backward, verbal fluency, semantic fluency, Stroop, and attentional measures (Hanagasi et al, 2011).…”

Acute and chronic cognitive effects of levodopa and dopamine agonists on patients with Parkinson’s disease: a review

“…This issue is of particular clinical interest considering that since the time of clinical diagnosis of PD many patients present a mild cognitive impairment: is this cognitive feature worsened or improved by the prolonged dopaminergic therapy? In addition to the potential risk of inducing dyskinesia and behavioral side effects such as impulse control disorders [Weintraub et al 2010], also cognitive effects of prolonged dopaminergic treatments should be taken into account by clinicians in order to anticipate or to delay their prescription to PD patients, possibly adopting other drugs with possible effects of neuroprotection and cognitive enhancement, as the selective monoamine oxidase type-B inhibitor rasagiline [Elmer et al 2006;Hanagasi et al 2011;Jenner and Langston, 2011].…”

Treatment of Cognitive, Psychiatric, and Affective Disorders Associated with Parkinson's Disease

“…A pilot study of donepezil for 10 PD patients with dysexecutive alterations without dementia reported improvement [15]. Rasagiline, a monoamine oxidase-B inhibitor (MAOB-I), was examined in a study of PD patients with cognitive deficits, but not PDD, and there was improvement of some measures of attention, suggesting a positive impact on executive function [16]. A longer-term study is ongoing (NCT013823420).…”