The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson’s disease

Broussolle, Emmanuel; Dentresangle, Christine; Landais, P.; Garcia-Larrea, Luis; Pollak, Pierre; Croisile, Bernard; Hibert, O.; Bonnefoi, Fréderic; Galy, G.; Froment, J; Comar, D.

doi:10.1016/s0022-510x(99)00127-6

Cited by 147 publications

(86 citation statements)

References 61 publications

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“…In an FDOPA study employing principle component analysis, impaired FDOPA utilization segregated with motor symptoms, but not cognitive function and mood of Parkinson's patients without diagnosis of major depression (Broussolle and others 1999). This would seem to exclude important contributions of nigrostriatal degeneration per se to declining cognitive function and mood in patients with Parkinson's disease.…”

Section: Personality and Cognitionmentioning

confidence: 88%

“…Even in advanced Parkinson's disease, the FDOPA influx was less impaired in the caudate nucleus (-45%) than in the putamen (-64%; Broussolle and others 1999). Elevated FDOPA utilization in the frontal cortex has been described in PET studies of early Parkinson's disease (Bruck and others 2005;Rakshi and others 1999), more notably in women than in men (Kaasinen and others 2001b).…”

Section: Acquired Parkinsonism and Idiopathic Parkinson's Diseasementioning

confidence: 94%

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PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches

2009

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[18F]Fluoro-3,4-dihydroxyphenyl-L-alanine (FDOPA) was one of the first successful tracers for molecular imaging by positron emission tomography (PET), and has proven immensely valuable for studies of Parkinson’s disease. Following intravenous FDOPA injection, the decarboxylated metabolite [18F] fluorodopamine is formed and trapped within terminals of the nigrostriatal dopamine neurons; reduction in the simple ratio between striatum and cerebellum is indicative of nigrostriatal degeneration. However, the kinetic analysis of dynamic FDOPA-PET recordings is formidably complex due to the entry into brain of the plasma metabolite O-methyl-FDOPA and due to the eventual washout of decarboxylated metabolites. Linear graphical analysis relative to a reference tissue input function is popular and convenient for routine clinical studies in which serial arterial blood samples are unavailable. This simplified approach has facilitated longitudinal studies in large patient cohorts. Linear graphical analysis relative to the metabolite-corrected arterial FDOPA input yields a more physiological index of FDOPA utilization, the net blood-brain clearance. Using a constrained compartmental model, FDOPA-PET recordings can be used to calculate the relative activity of the enzyme DOPA decarboxylase in living brain. We have extended this approach so as to obtain an index of steady-state trapping of [ 18F]fluorodopamine in synaptic vesicles. Although simple methods of image analysis are sufficient for the purposes of routine clinical studies, the more complex approaches have revealed hidden aspects of brain dopamine in personality, healthy aging, and in the pathophysiologies of Parkinson’s disease and schizophrenia.

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Section: Personality and Cognitionmentioning

confidence: 88%

Section: Acquired Parkinsonism and Idiopathic Parkinson's Diseasementioning

confidence: 94%

PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches

2009

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“…Reduced ¹⁸F-fl uorodopa uptake in the caudate has been associated with executive dysfunction in patients with PD in some 92,93 but not all studies, 94 thus implicating nigrostriatal dopamine depletion in these cognitive defi cits. The mesocortical dopamine system is also aff ected, 95 although prefrontal overactivity, particularly in the anterior cingulate, has been found at early stages of the disease.…”

Section: Pathophysiology Of Executive Dysfunctionmentioning

confidence: 99%

Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms

Rodriguez-Oroz

Jahanshahi

Krack

et al. 2009

The Lancet Neurology

745

500

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A dopaminergic defi ciency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a defi ciency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine defi ciency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic defi cit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic defi ciency in the early phase of the parkinsonian state and the diff erent circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.

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“…The 18F-dopa rate constant Ki was reduced in the caudate nucleus (0.011 down to 0.0043) and inversely correlated with an increase in the UPDRS from 11.9 AE 5.2 to 50 AE 11.6 (Broussolle et al, 1999).…”

Section: Monkey In Vivo Modelsmentioning

confidence: 91%

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

Ockleford¹,

Adriaanse²,

Berny³

et al. 2017

EFS2

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In 2013, EFSA published a literature review on epidemiological studies linking exposure to pesticides and human health outcome. As a follow up, the EFSA Panel on Plant Protection Products and their residues (PPR Panel) was requested to investigate the plausible involvement of pesticide exposure as a risk factor for Parkinson's disease (PD) and childhood leukaemia (CHL). A systematic literature review on PD and CHL and mode of actions for pesticides was published by EFSA in 2016 and used as background documentation. The Panel used the Adverse Outcome Pathway (AOP) conceptual framework to define the biological plausibility in relation to epidemiological studies by means of identification of specific symptoms of the diseases as AO. The AOP combines multiple information and provides knowledge of biological pathways, highlights species differences and similarities, identifies research needs and supports regulatory decisions. In this context, the AOP approach could help in organising the available experimental knowledge to assess biological plausibility by describing the link between a molecular initiating event (MIE) and the AO through a series of biologically plausible and essential key events (KEs). As the AOP is chemically agnostic, tool chemical compounds were selected to empirically support the response and temporal concordance of the key event relationships (KERs). Three qualitative and one putative AOP were developed by the Panel using the results obtained. The Panel supports the use of the AOP framework to scientifically and transparently explore the biological plausibility of the association between pesticide exposure and human health outcomes, identify data gaps, define a tailored testing strategy and suggests an AOP's informed Integrated Approach for Testing and Assessment (IATA).

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The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson’s disease

Cited by 147 publications

References 61 publications

PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches

PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches

Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

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