Objective: To describe the frequency of mild cognitive impairment (MCI) in Parkinson disease (PD) in a cohort of newly diagnosed incident PD cases and the associations with a panel of biomarkers.Methods: Between June 2009 and December 2011, 219 subjects with PD and 99 age-matched controls participated in clinical and neuropsychological assessments as part of a longitudinal observational study. Consenting individuals underwent structural MRI, lumbar puncture, and genotyping for common variants of COMT, MAPT, SNCA, BuChE, EGF, and APOE. PD-MCI was defined with reference to the new Movement Disorder Society criteria.Results: The frequency of PD-MCI was 42.5% using level 2 criteria at 1.5 SDs below normative values. Memory impairment was the most common domain affected, with 15.1% impaired at 1.5 SDs. Depression scores were significantly higher in those with PD-MCI than the cognitively normal PD group. A significant correlation was found between visual Pattern Recognition Memory and cerebrospinal b-amyloid 1-42 levels (b standardized coefficient 5 0.350; p 5 0.008) after controlling for age and education in a linear regression model, with lower b-amyloid 1-42 and 1-40 levels observed in those with PD-MCI. Voxel-based morphometry did not reveal any areas of significant gray matter loss in participants with PD-MCI compared with controls, and no specific genotype was associated with PD-MCI at the 1.5-SD threshold. Conclusions:In a large cohort of newly diagnosed PD participants, PD-MCI is common and significantly correlates with lower cerebrospinal b-amyloid 1-42 and 1-40 levels. Future longitudinal studies should enable us to determine those measures predictive of cognitive decline.
Previous research has noted that music can improve gait in several pathological conditions, including Parkinson's disease, Huntington's disease and stroke. Current research into auditory-motor interactions and the neural bases of musical rhythm perception has provided important insights for developing potential movement therapies. Specifically, neuroimaging studies show that rhythm perception activates structures within key motor networks, such as premotor and supplementary motor areas, basal ganglia and the cerebellum - many of which are compromised to varying degrees in Parkinson's disease. It thus seems likely that automatic engagement of motor areas during rhythm perception may be the connecting link between music and motor improvements in Parkinson's disease. This review seeks to describe the link, address core questions about its underlying mechanisms, and examine whether it can be utilized as a compensatory mechanism.
BackgroundDopaminergic drugs remain the mainstay of Parkinson’s disease therapy but often fail to improve cognitive problems such as impulsivity. This may be due to the loss of other neurotransmitters, including noradrenaline, which is linked to impulsivity and response inhibition. We therefore examined the effect of the selective noradrenaline reuptake inhibitor atomoxetine on response inhibition in a stop-signal paradigm.MethodsThis pharmacological functional magnetic resonance imaging study used a double-blinded randomized crossover design with low-frequency inhibition trials distributed among frequent Go trials. Twenty-one patients received 40 mg atomoxetine or placebo. Control subjects were tested on no-drug. The effects of disease and drug on behavioral performance, regional brain activity, and functional connectivity were analyzed using general linear models. Anatomical connectivity was examined using diffusion-weighted imaging.ResultsPatients with Parkinson’s disease had longer stop-signal reaction times, less stop-related activation in the right inferior frontal gyrus (RIFG), and weaker functional connectivity between the RIFG and striatum compared with control subjects. Atomoxetine enhanced stop-related RIFG activation in proportion to disease severity. Although there was no overall behavioral benefit from atomoxetine, analyses of individual differences revealed that enhanced response inhibition by atomoxetine was associated with increased RIFG activation and functional frontostriatal connectivity. Improved performance was more likely in patients with higher structural frontostriatal connectivity.ConclusionsThis study suggests that enhanced prefrontal cortical activation and frontostriatal connectivity by atomoxetine may improve response inhibition in Parkinson’s disease. These results point the way to new stratified clinical trials of atomoxetine to treat impulsivity in selected patients with Parkinson’s disease.
See Dujardin (doi:) for a scientific commentary on this article. Nombela et al. present data from the ICICLE-PD study of cognition in newly diagnosed Parkinson’s disease. Consistent with the ‘Dual Syndrome’ hypothesis, impairments in executive function reflect a frontal dopaminergic syndrome modulated by COMT genotype, while visuospatial and memory deficits reflect disruption of temporo-parietal systems modulated by MAPT and APOE.
Impulsivity is common in Parkinson’s disease. In a double-blind, placebo-controlled study with multi-modal imaging, Ye et al. reveal improved response inhibition in some patients receiving the SSRI citalopram, including those with advanced disease. Improvements correlated with preserved frontostriatal structural connectivity and drug-induced prefrontal activity, highlighting the need for patient stratification in trials.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.