Cognitive Impairment and the Brain Dopaminergic System in Parkinson Disease

Rinne, Juha O.; Portin, Raija; Ruottinen, Hanna; Nurmi, Elina; Bergman, Jörgen; Haaparanta, Merja; Solin, Olof

doi:10.1001/archneur.57.4.470

Cited by 320 publications

(204 citation statements)

References 45 publications

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“…Thus, in a PET study of dopamine transporters, binding in the caudate nucleus correlated inversely with sequence learning in PD patients (Carbon et al, 2004). In earlier FDOPA/PET studies, k 3 s in the caudate of PD patients correlated inversely with performance of a memory task (Holthoff-Detto et al, 1997), somatosensory discrimination (Weder et al, 1999), and the Stroop interference task (Rinne et al, 2000;Brü ck et al, 2001). We now use quantitative parametric methods to reveal an increased elimination rate constant for [ 18 F]fluorodopamine in the most affected caudate nucleus of patients with early PD, predicting that cognitive processes may be influenced by asymmetric changes in dopamine turnover.…”

Section: Discussionmentioning

confidence: 87%

Dopamine Storage Capacity in Caudate and Putamen of Patients with Early Parkinson's Disease: Correlation with Asymmetry of Motor Symptoms

Kumakura

Gjedde

Danielsen

et al. 2005

J Cereb Blood Flow Metab

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Conventional graphical analysis of positron emission tomography (PET) recordings of the cerebral uptake of the DOPA decarboxylase substrate [ 18 F]fluorodopa (FDOPA) assumes irreversible trapping of [ 18 F]fluorodopamine formed in the brain. However, 4-h long PET recordings allow the estimation of a rate constant for elimination of [ 18 F]fluorodopamine from the brain (k loss ), from which can be calculated an effective distribution volume (EDV 1 ), which is an index of [ 18 F]fluorodopamine storage capacity. We earlier developed a method employing 2-h long FDOPA recordings for the estimation of k loss and EDV, here defined as EDV 2 . This method is based on subtraction of the calculated brain concentrations of the FDOPA metabolite O-methyl-FDOPA, rather than the subtraction of the entire radioactivity in a reference region. We now extend this method for the parametric mapping of these parameters in the brain of healthy aged volunteers and patients with Parkinson's disease (PD), with asymmetry of motor symptoms. For parametric mapping, we use a novel application of a multilinear solution for the two-tissue compartment FDOPA model. We also test a new application of the Logan graphical analysis for mapping of the FDOPA distribution volume at equilibrium. The estimates of k loss and EDV 2 were more sensitive for the discrimination of biochemical abnormality in the putamen of patients with early PD relative to healthy aged subjects, than was the conventional net influx estimate. Of the several methods, multilinear estimates of EDV 2 were most sensitive for discrimination of PD and normal putamen. However, k loss was most sensitive for detecting biochemical asymmetry in the putamen of PD patients, and only k loss also detected in the caudate of PD patients a decline in the retention of [ 18 F]fluorodopamine relative to healthy aged control subjects.

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Section: Discussionmentioning

confidence: 87%

Dopamine Storage Capacity in Caudate and Putamen of Patients with Early Parkinson's Disease: Correlation with Asymmetry of Motor Symptoms

Kumakura

Gjedde

Danielsen

et al. 2005

J Cereb Blood Flow Metab

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“…In this study we also demonstrate a single chemical (NAA)-cognitive network in the brain, specifically in ACC, as a possible neurobiological/neurochemical mechanism for development of cognitive interference. Given that the SCW interference has been found abnormal in several neuropsychiatric disorders, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] this neuroimaging/cognitive tool may be useful for documentation of interference in studying cognitive control mechanisms in general, and in diagnosis of neuropsychiatric disorders particularly where dysfunction of cingulate cortex is expected. Another valuable application of these findings might be a new drug development in the pharmaceutical industry to design new chemical compounds and drugs which would produce brain changes that would be reflected in the interference and NAA measures (eg, in attention deficit hyperactivity disorder, where dysfunction of the ACC was already revealed by fMRI and the Counting Stroop; 4 or in obsessive-compulsive disorder, where reduced levels of cingulate NAA have been found using 1 H-MRS 48 ) and as an imaging tool to study effects of these chemical compounds and drugs (eg, as a guide in pre-clinical and early clinical development of drug candidates, and as proof of the effectiveness of new drugs as well as decisions on their future development).…”

Section: Discussionmentioning

confidence: 99%

“…For example, a color word such as blue that appears in an ink color such as red may inhibit naming of the color red due to automatic perception of incompatible information (such as color word blue). Previous studies of the Stroop effect provides convincing evidence that cognitive interference is abnormal in various neuropsychiatric disorders such as attention deficit hyperactivity disorder, 3,4 schizophrenia, 5-9 depression, 10,11 anxiety disorders, [12][13][14][15] Parkinson's disease, 16 Alzheimer's disease, 17 and HIV disease. 18 New imaging technologies, including positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have determined which functional circuitry in the brain is engaged in interference.…”

Section: Introductionmentioning

confidence: 92%

Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo 1H-MRS study of the Stroop Color-Word task

et al. 2001

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The neurobiology of cognitive interference is unknown. Previous brain imaging studies using the Stroop Color-Word (SCW) task indicate involvement of the cingulate cortex cognitive division. The present study examines interrelationships between regional brain N-Acetyl aspartate (NAA) levels (as identified by in vivo proton magnetic resonance spectroscopy in the right and left anterior cingulate cortex (ACC), dorsolateral prefrontal cortex, orbitofrontal cortex and thalamus) and cognitive interference (as measured by the SCW task) in 15 normal subjects. The results show that brain chemistry depends on cognitive interference levels (high vs low). Reduction of NAA levels was demonstrated in the right ACC (ie, cognitive midsupracallosal division) of high interference subjects, as compared to the low interference group (P Ͻ 0.01, two-tailed t-test). Chemical-cognitive relationships were analyzed by calculating correlations between regional NAA levels and the SCW task scores. Cognitive interference was highly correlated with the right anterior cingulate NAA (r = 0.76, P Ͻ 0.001), and was unrelated to other studied regional NAA, including the left ACC (P Ͻ 0.025; comparing the difference between r values in the right and left ACC). The interrelationships between NAA across brain regions were examined using correlation analysis (square matrix correlation maps), which detected different connectivity patterns between the two groups. These findings provide evidence of ACC involvement in cognitive interference suggesting a possibility of neuronal reorganization in the physiological mechanism of interference (most likely due to genetically predetermined control of the number of neurons, dendrites and receptors, and their function). We conclude that spectroscopic brain mapping of NAA, the marker of neuronal density and function, to the SCW task measures differentiates between high and low interference in normal subjects. This neuroimaging/cognitive tool may be useful for documentation of interference in studying cognitive control mechanisms, and in diagnosis of neuropsychiatric disorders where dysfunction of cingulate cortex is expected. Molecular Psychiatry (2001) 6, 529-539.

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“…The risk of dementia significantly increases with age. Cholinergic deficits and cortical Lewy bodies have been associated with the occurrence of PD dementia (PDD), while cognitive impairments are most likely due to the early and progressive degeneration of monoaminergic systems to associative cortical and subcortical regions (Rinne et al, 2000;Emre, 2003). Acetylcholinesterase inhibitors are first-line therapy in patients with PDD.…”

Section: Therapeutics For Nonmotor Symptoms Of Pdmentioning

confidence: 99%

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Smith

Wichmann

Factor

et al. 2011

Neuropsychopharmacol

194

137

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The demonstration that dopamine loss is the key pathological feature of Parkinson's disease (PD), and the subsequent introduction of levodopa have revolutionalized the field of PD therapeutics. This review will discuss the significant progress that has been made in the development of new pharmacological and surgical tools to treat PD motor symptoms since this major breakthrough in the 1960s. However, we will also highlight some of the challenges the field of PD therapeutics has been struggling with during the past decades. The lack of neuroprotective therapies and the limited treatment strategies for the nonmotor symptoms of the disease (ie, cognitive impairments, autonomic dysfunctions, psychiatric disorders, etc.) are among the most pressing issues to be addressed in the years to come. It appears that the combination of early PD nonmotor symptoms with imaging of the nigrostriatal dopaminergic system offers a promising path toward the identification of PD biomarkers, which, once characterized, will set the stage for efficient use of neuroprotective agents that could slow down and alter the course of the disease.

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Cognitive Impairment and the Brain Dopaminergic System in Parkinson Disease

Cited by 320 publications

References 45 publications

Dopamine Storage Capacity in Caudate and Putamen of Patients with Early Parkinson's Disease: Correlation with Asymmetry of Motor Symptoms

Dopamine Storage Capacity in Caudate and Putamen of Patients with Early Parkinson's Disease: Correlation with Asymmetry of Motor Symptoms

Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo 1H-MRS study of the Stroop Color-Word task

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

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