Effects of dopaminergic treatment on striatal dopamine turnover in de novo Parkinson disease

Storch, Alexander; Wolz, Martin; Beuthien‐Baumann, Bettina; Löhle, Matthias; Herting, Birgit; Schwanebeck, Uta; Oehme, Liane; Hoff, Jörg van den; Perick, Maria; Grählert, Xina; Kotzerke, Jörg; Reichmann, Heinz

doi:10.1212/wnl.0b013e3182918c2d

Cited by 22 publications

(28 citation statements)

References 36 publications

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“…By reading the full text of the remaining 67 articles, 29 studies were excluded because a result of without control groups, 24 were excluded because of not testing the effect of comparing L-dopa alone with L-dopasparing therapy in early PD patients, three studies were eliminated due to short time follow-up. Ultimately, just leaving 11 qualified studies satisfied the pre-established inclusion criteria [10,[13][14][15][16][17][18][19][20][21][22] (Fig. 1).…”

Section: Results Study Inclusionmentioning

confidence: 99%

“…The mean age of those included studies was relatively young at about 60 years, most were in Hoehn and Yahr stage I or II and there were slightly more males than females. The number of participants included in this meta-analysis ranged from 35 [22] to 1406 [10] subjects. Meanwhile, the time of follow-up was ranged from 1 year [22] to 10 years [19].…”

Section: Description Of Studiesmentioning

confidence: 99%

“…The number of participants included in this meta-analysis ranged from 35 [22] to 1406 [10] subjects. Meanwhile, the time of follow-up was ranged from 1 year [22] to 10 years [19]. L-Dopa-sparing in this study including dopamine agonists or MAOBI, but only one trial used MAOBI [10], the remaining trials adopted dopamine agonists.…”

Section: Description Of Studiesmentioning

confidence: 99%

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Levodopa alone compared with levodopa-sparing therapy as initial treatment for Parkinson’s disease: a meta-analysis

Xie

Zhang²,

Wang

et al. 2015

Neurol Sci

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To assess the long-term use of L-dopa alone vs L-dopa-sparing therapy, as initial treatment, provides the most efficient long-term control of symptoms and best quality of life for people with early Parkinson's disease (PD). PubMed; Google scholar; Cochrane Central Register of Controlled Trials and the Web of Science were searched for randomised, placebo-controlled trials (RCTs) on L-dopa alone and L-dopa sparing as initial treatment in early PD patients. We used a random effects model rather than a fixed effects model because of this takes into account heterogeneity between multi-studies. Eleven RCTs were included. The results showed that L-dopa alone could evidently improve the UPDRS part I (p = 0.005), part II (p < 0.0001), part III (p < 0.0001) and UPDRS total score (p = 0.004) compared with L-dopa-sparing therapy in PD patients. Meanwhile, a reduced risk of dyskinesia (p < 0.0001, RR = 1.88, 95 % CI 1. 37-2.59) and wearing-off phenomenon (p < 0.00001, RR = 1.36, 95 % CI 1. 20-1.55) in patients treated initially with L-dopa-sparing therapy compared to L-dopa has been consistently reported. What is more, we found more patients on aL-dopa-sparing therapy were more than triple as likely to discontinue treatment prematurely due to adverse events than L-dopa treatment patients (43.7 vs 15.8 %). L-Dopa alone is the most effective medication available for treating the motor symptoms of PD patients, despite the greater incidence of involuntary movements. Meanwhile, more patients on dopamine agonists or MAOBI were more likely to discontinue treatment prematurely than L-dopa alone treatment patients within the long follow-up period.

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Section: Results Study Inclusionmentioning

confidence: 99%

Section: Description Of Studiesmentioning

confidence: 99%

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Levodopa alone compared with levodopa-sparing therapy as initial treatment for Parkinson’s disease: a meta-analysis

Xie

Zhang²,

Wang

et al. 2015

Neurol Sci

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“…Extensive evidence indicates that both pre‐ and postsynaptic components of the dopaminergic system contribute to the development of LIDs. Presynaptic mechanisms of particular relevance include nigrostriatal dopaminergic neuronal loss3 that results in decreased dopamine buffering capacity, and increased extracellular dopamine levels that arise with levodopa treatment 4, 5…”

Section: Introductionmentioning

confidence: 99%

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Brumberg

Küsters

Al‐Momani

et al. 2017

Ann Clin Transl Neurol

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ObjectiveTo investigate the association between levodopa‐induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease.MethodsThis study included 13 Parkinson's disease patients with peak‐of‐dose levodopa‐induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5‐[123I]iodo‐3‐[2(S)‐2‐azetidinylmethoxy]pyridine single‐photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [123I]N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane single‐photon emission computed tomography, to measure dopamine reuptake transporter density and 2‐[18F]fluoro‐2‐deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed.ResultsDensity of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side.InterpretationOur findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic‐depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression.

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“…Like methylphenidate, cabergoline has been shown to be functionally active in the striatum (198), supporting the hypothesis that modulation of the D 2 mediated indirect pathway contributes to enhanced action cancellation behaviour. Dopamine receptor expressing striatal interneurons may also play an important role in regulating direct and indirect pathway neurons (199).…”

Section: Action Cancellationmentioning

confidence: 62%

Neurochemical and neurophysiological bases of executive control

Nandam¹

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The aim of this work is to further understanding into the biological bases of human executive control through an integration of neuropsychology, psychopharmacology and functional imaging. Executive control includes the prototypical executive functions of response inhibition and error awareness.Response inhibition can be further divided into action cancellation and action restraint, which were assayed with the stop signal (SST) and Error Awareness (EAT) tasks, respectively. The EAT, which is a modified go-no go paradigm, was also used to measure error awareness behaviour. Monoamine neurotransmitters, specifically dopamine, noradrenaline and serotonin, were modulated during task performance with acute doses of methylphenidate (a dopamine and noradrenaline reuptake inhibitor), atomoxetine (a noradrenaline reuptake inhibitor), citalopram (a serotonin reuptake inhibitor) and cabergoline (a D 2 agonist). The pharmacoimaging correlates of task performance were also examined with functional magnetic resonance imaging (fMRI). All experiments adhered to a randomised, double blind, placebo-controlled, crossover design and were limited to 18-35 year old healthy right-handed male participants.In Chapter 1, twenty-four (24) participants received acute doses of methylphenidate (30mg), atomoxetine (60mg), citalopram (30mg) and placebo and performed the SST. Methylphenidate, but not atomoxetine or citalopram, led to a reduction in response time variability and stop-signal reaction time indicating enhanced action cancellation compared with the other drug conditions. This enhancement occurred without change to overall response speed suggesting that methylphenidate was modulating core response inhibition processes rather than simply augmenting overall processing speed.This result argued for the prominence of dopaminergic, rather than adrenergic or serotonergic, mechanisms in action cancellation.In Chapter 2, the pharmacoimaging correlates of action restraint aspect were explored. Twenty-seven (27) males received acute doses of methylphenidate (30mg), atomoxetine (60mg), citalopram (30mg) and placebo whilst undertaking the EAT during fMRI. No-go related BOLD activations were then correlated for each of the drug conditions. Although Inhibitory performance under methylphenidate was numerically superior to the other drug conditions, this difference did not achieve statistical significance. On fMRI, methylphenidate activated, versus placebo, the anterior cingulate cortex, right inferior frontal, left middle frontal, left angular and right superior temporal gyri and right caudate. Atomoxetine activated a broad network of cortical regions.Both methylphenidate and atomoxetine, but not citalopram, activated superior temporal, right inferior frontal and left middle frontal clusters. Citalopram only activated the left inferior occipital lobe. Taking each condition's activations as functionally defined regions of interest, the specificity of no-go related activity was compared across the four conditions. Only methylphenidate demonstrat...

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Effects of dopaminergic treatment on striatal dopamine turnover in de novo Parkinson disease

Cited by 22 publications

References 36 publications

Levodopa alone compared with levodopa-sparing therapy as initial treatment for Parkinson’s disease: a meta-analysis

Levodopa alone compared with levodopa-sparing therapy as initial treatment for Parkinson’s disease: a meta-analysis

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Neurochemical and neurophysiological bases of executive control

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