Abstract
Objectives To evaluate the effects of atomoxetine on complex attention and other neurocognitive domains in idiopathic Parkinson's disease (PD). Methods Interventional trials reporting changes in complex attention and other neurocognitive functions (Diagnostic and Statistical Manual of Mental Disorders-5) following administration of atomoxetine for at least 8 weeks in adults with idiopathic PD were included. Effect sizes (Cohen's d), the standardized mean difference in the scores of each cognitive domain, were compared using a random-effects model (MetaXL version 5.3). Results Three studies were included in the final analysis. For a change in complex attention in PD with mild cognitive impairment (MCI), the estimated effect size was small and nonsignificant (0.16 (95% CI: −0.09, 0.42), n = 42). For changes in executive function, perceptual-motor function, language, social cognition, and learning and memory, the estimated effect sizes were small and medium, but nonsignificant. A deteriorative trend in executive function was observed after atomoxetine treatment in PD with MCI. For a change in global cognitive function in PD without MCI, the estimated effect size was large and significant. Conclusion In idiopathic PD with MCI, atomoxetine does not improve complex attention. Also, a deteriorative trend in the executive function was noted.
Highlights
Locus coeruleus (LC) is a small pontine nucleus of about 15,000 noradrenergic neurons innervating a large number of cortical and subcortical areas in the brain, for many of which, it is the only source of norepinephrine [1]
Completed and published interventional trials investigating the effects of atomoxetine on cognitive functions in idiopathic Parkinson’s disease (PD) were included. e inclusion criteria were as follows: interventional studies that included patients of age ≥18 years of either gender, diagnosed with idiopathic PD, and patients who had received atomoxetine of any dose for at least 8 weeks, and any domain of cognitive function was reported using any scale irrespective of statistical significance. e exclusion criteria were initiation or change in dose of any confounding comedication after initiating treatment with atomoxetine. e primary outcome of the study was the change in clinical score in any individual domain of cognitive function (DSM5) [19]
MEDLINE/PubMed, IndMED, and Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL) and Cochrane Methodology Register) were searched until 28 November 2019. e search terms used in various combinations were “atomoxetine,” “cognition,” “cognitive therapy,” “cognitive function,” “idiopathic Parkinson’s disease,” “iPD,” “Parkinson’s disease,” “PD,” “neurodegenerative disease,” “mild cognitive impairment,” and “MCI.” ese search terms were adapted for use with different bibliographic databases in combination with database-specific filters for studies, if available. e search strategy was used to obtain titles and abstracts of relevant
Summary
Locus coeruleus (LC) is a small pontine nucleus of about 15,000 noradrenergic neurons innervating a large number of cortical and subcortical areas in the brain, for many of which, it is the only source of norepinephrine [1] It serves as the major noradrenergic supply to the forebrain including the prefrontal cortex and is critically important for cognitive functions [2, 3]. Idiopathic Parkinson’s disease (PD) is a neurodegenerative disorder, primarily characterized by bradykinesia, rigidity, and tremor [7]. It results from the degeneration of dopaminergic neurons in the substantia nigra caused by the accumulation of misfolded α-synuclein into Lewy neurites and Lewy bodies [7]. Some of these features include autonomic and olfactory deficits, depression, and sleep disturbances along with emotional disorders [10]
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