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Donald B. Calne - One of the best experts on this subject based on the ideXlab platform.

  • Contributions of Positron Emission Tomography to elucidating the pathogenesis of Idiopathic Parkinsonism and Dopa Responsive Dystonia
    Journal of neural transmission. Supplementum, 1997
    Co-Authors: Donald B. Calne, R. De La Fuente-fernandez, Asha Kishore
    Abstract:

    The metabolic mapping of brain activity, using PET, confirms the conventional wisdom of neurophysiology. In studies of pathophysiology, PET has yielded evidence that has generated new hypotheses. Progression of the lesion detectable with Fluorodopa, in human subjects exposed to MPTP, raises the possibility of a transient environmental event being a cause of progressive neurodegeneration. Studies with Fluorodopa in Idiopathic Parkinsonism indicate that the rate of loss of neurons is faster initially, and then tends to approach the normal age-related decline. In dopa responsive dystonia, the finding of normal Fluorodopa PET led to the prediction that the lesion would be functional rather than anatomical; this has been confirmed by the identification of a defect in dopamine synthesis in this disorder. Filally, new PET ligands show promise for future studies designed to unravel the pathogenesis of diseases involving the basal ganglia.

  • Longitudinal Fluorodopa positron emission tomographic studies of the evolution of idiopathic parkinsonism
    Annals of neurology, 1994
    Co-Authors: Francois J G Vingerhoets, Barry J. Snow, Chong S. Lee, Michael Schulzer, Edwin Mak, Donald B. Calne
    Abstract:

    Previous estimates of the rate of progression of the nigral pathology underlying idiopathic parkinsonism (IP) have been derived mainly from pathological studies that have an inherent selection bias. Fluorodopa positron emission tomography (PET) is a reliable tool for assessing nigrostriatal dopaminergic function in vivo. We performed Fluorodopa PET on two occasions, 7 years apart, on 16 patients with IP (age at the time of the first scan, 51 +/- 14 yr [mean +/- SD]) and 10 normal controls (age, 54 +/- 16 yr). For the patients with IP, the average duration of symptoms from the time of diagnosis to the first scan was 4.5 years (range, 1-12 yr); their PET index (striatal-occipital)/occipital ratio, dropped by 1.7% per year, from 0.49 +/- 0.08 to 0.43 +/- 0.08 (p < 0.001). The normals' ratio decreased by 0.3% per year from 0.77 +/- 0.05 to 0.75 +/- 0.10 (p = 0.33). The ratios in the IP group progressed significantly faster than the controls (p = 0.036). The rate of decline in IP represents 7.8% per decade, expressed as a fraction of the normals' initial mean value at 54 years of age. These results also permit power analysis for the design of future studies assessing the effect of treatment on the underlying pathology in IP.

  • Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning
    Lancet (London England), 1993
    Co-Authors: H. Takahashi, Barry J. Snow, R.f. Peppard, Andrew Eisen, M. H. Bhatt, Donald B. Calne
    Abstract:

    Although rare, the chronic neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and idiopathic parkinsonism coexist to a greater degree than expected by chance. This suggests that patients with ALS may have subclinical lesions of the nigrostriatal dopaminergic pathway. To study this hypothesis, we did positron emission tomography with 6-Fluorodopa on 16 patients with sporadic ALS and without extrapyramidal disease, and compared the results with age-matched controls. We found a significant progressive fall in 6-Fluorodopa uptake with time since diagnosis, and reduced dopaminergic function in 3 patients with ALS of long duration. This supports the hypothesis that ALS and IP may share pathogenesis and, perhaps, aetiology.

  • The transport of L-6-Fluorodopa and its metabolites from blood to cerebrospinal fluid and brain.
    Annals of neurology, 1993
    Co-Authors: John P. Hammerstad, Thomas J. Ruth, B. D. Pate, Kellie A. Hewitt, Grace L.-y. Chan, Donald B. Calne
    Abstract:

    The transport of L-6-Fluorodopa and its major metabolites from the blood to the brain, cerebrospinal fluid (CSF), and muscle was studied in carbidopa-pretreated cynomolgus monkeys. A bolus intravenous injection of 18F-L-6-Fluorodopa was followed by serial positron emission tomography scans and sampling of cisternal CSF and arterial blood. The relative concentrations of L-6-Fluorodopa and its metabolites were determined in blood plasma and CSF by high-performance liquid chromatography. Raising the blood concentration of phenylalanine by intraperitoneal injection markedly reduced the accumulation of tracer in the brain. This indicates that L-6-Fluorodopa and 3-O-methylFluorodopa, like native L-dopa and its O-methylated derivative, are transported at the brain capillary by the large neutral amino acid carrier-mediated system, which is subject to saturation and competition by other large neutral amino acids (such as phenylalanine) at physiological plasma concentrations. In contrast, administration of phenylalanine had no effect on the accumulation of tracer either in muscle, or as L-6-Fluorodopa and 3-O-methylFluorodopa, in CSF. This suggests that the transport of L-dopa and its derivatives at the blood-CSF barrier differs from the transport at the blood-brain barrier and also that measurement of CSF L-dopa is not a good index of the transport and pharmacokinetics of L-dopa in the brain. However, the effect of phenylalanine administration in reducing the concentration of fluorohomovanillic acid in the CSF suggests that the concentration of homovanillic acid in the CSF is an accurate reflection of dopamine turnover in the brain.

  • Human positron emission tomographic [18F]Fluorodopa studies correlate with dopamine cell counts and levels
    Annals of neurology, 1993
    Co-Authors: Barry J. Snow, Donald B. Calne, H. Takahashi, Ikuo Tooyama, Edith G. Mcgeer, Tatsuo Yamada, Hiroshi Kimura
    Abstract:

    Postmortem counts of dopaminergic cell densities in the substantia nigra (5 subjects) and striatal levels of dopamine (DA) and its metabolites (6 subjects) were determined on 1 parkinsonian (PD), 3 progressive supranuclear palsy (PSP), 1 amyotrophic lateral sclerosis, and 1 Alzheimer's case who had been positron emission tomography scanned with 6-[18F]Fluorodopa during life. [18F]Fluorodopa uptake rate constants, which presumably depend on the number of functioning striatal DA terminals, were strictly proportional to cell densities (significant correlation with zero intercept) and also correlated significantly with striatal DA levels but with an intercept indicating greater losses of DA than of terminals in PSP and PD. Postmortem data on 6 PD, 1 PSP, and 9 neuronally normal controls substantiated the significant correlation between cell counts and DA levels, with the latter being the more depressed in pathological cases.

Francois J G Vingerhoets - One of the best experts on this subject based on the ideXlab platform.

  • bilateral fetal nigral transplantation into the postcommissural putamen in parkinson s disease
    Annals of Neurology, 1995
    Co-Authors: Thomas B Freeman, Cesario V. Borlongan, Paul R. Sanberg, Robert A. Hauser, Warren C Olanow, Michael G Nauert, Donald A Smith, Douglas A Holt, Jeffrey H Kordower, Francois J G Vingerhoets
    Abstract:

    We performed fetal nigral transplantations in 4 Parkinson's disease (PD) patients. Solid grafts were bilaterally implanted into the postcommissural putamen using 3 to 4 donors per side aged 6 1/2 to 9 weeks postconception. Transplant deposits were separated by no more than 5 mm in three dimensions. Cyclosporine was employed for a total of 6 months. Patients were evaluated at baseline and at 1, 3, and 6 months postoperatively. Striatal 18-Fluorodopa uptake was assessed by positron emission tomography at baseline and at 6 months postoperatively. The procedure was well tolerated in all patients. One patient had a clinically asymptomatic superficial cortical hemorrhage along the needle tract and a second had transient postoperative confusion and hallucinations. All patients experienced clinically meaningful benefit. Significant improvement (p < 0.05) was detected in total UPDRS score during the „off” state, Schwab-England disability score during the „off” state, percent „off” time, and percent „on” time with dyskinesia. Increased striatal Fluorodopa uptake was observed bilaterally in each patient, with mean increases of 53% on the right (p = 0.01) and 33% on the left (p = 0.08). Our study demonstrated clear and consistent improvement in clinical features and striatal Fluorodopa uptake following fetal tissue transplantation in patients with advanced PD whose condition was not improved preoperatively by drug manipulation. These preliminary results are encouraging and support further studies to evaluate grafting strategies as a therapy for PD.

  • neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with parkinson s disease
    The New England Journal of Medicine, 1995
    Co-Authors: Jeffrey H Kordower, Thomas B Freeman, Paul R. Sanberg, Robert A. Hauser, Michael G Nauert, Donald A Smith, Francois J G Vingerhoets, B J Snow, Elliott J Mufson, Daniel P Perl
    Abstract:

    Background Trials are under way to determine whether fetal nigral grafts can improve motor function in patients with Parkinson's disease. Some studies use Fluorodopa uptake on positron-emission tomography (PET) as a marker of graft viability, but Fluorodopa uptake does not distinguish between host and grafted neurons. There has been no direct evidence that grafts of fetal tissue can survive and innervate the striatum. Methods We studied a 59-year-old man with advanced Parkinson's disease who received bilateral grafts of fetal ventral mesencephalic tissue in the postcommissural putamen. The tissue came from seven embryos between 61/2 and 9 weeks after conception. The patient died 18 months later from a massive pulmonary embolism. The brain was studied with the use of tyrosine hydroxylase immunohistochemical methods. Results After transplantation, the patient had sustained improvement in motor function and a progressive increase in Fluorodopa uptake in the putamen on PET scanning. On examination of the brai...

  • neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with parkinson s disease
    The New England Journal of Medicine, 1995
    Co-Authors: Jeffrey H Kordower, Thomas B Freeman, Paul R. Sanberg, Robert A. Hauser, Donald A Smith, Francois J G Vingerhoets, B J Snow, Elliott J Mufson, G M Nauert, Daniel P Perl
    Abstract:

    Background Trials are under way to determine whether fetal nigral grafts can improve motor function in patients with Parkinson's disease. Some studies use Fluorodopa uptake on positron-emission tomography (PET) as a marker of graft viability, but Fluorodopa uptake does not distinguish between host and grafted neurons. There has been no direct evidence that grafts of fetal tissue can survive and innervate the striatum. Methods We studied a 59-year-old man with advanced Parkinson's disease who received bilateral grafts of fetal ventral mesencephalic tissue in the postcommissural putamen. The tissue came from seven embryos between 61/2 and 9 weeks after conception. The patient died 18 months later from a massive pulmonary embolism. The brain was studied with the use of tyrosine hydroxylase immunohistochemical methods. Results After transplantation, the patient had sustained improvement in motor function and a progressive increase in Fluorodopa uptake in the putamen on PET scanning. On examination of the brai...

  • An aging effect in striatal Fluorodopa uptake? Large versus small ROIs.
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 1994
    Co-Authors: Barry J. Snow, Francois J G Vingerhoets, W.r. Wayne Martin
    Abstract:

    To the Editor: We read with interest the paper by Eidelberg et ai. (1993), in which the authors state that they ana­ lyzed the scans according to our method. Unfortu­ nately, they did not. We used elliptical striatal regions of interest (ROIs) in our original paper and found a clear aging effect (Martin et aI., 1989). Eidelberg et ai. used rectangular ROIs in their attempt to replicate our method. The difference may be critical, as rectan­ gular ROIs would necessarily include more ventri­ cle, where there is no background activity, than el­ liptical ROIs; the error introduced by this may ob­ scure any aging effect. Eidelberg et ai. concede in their article that their failure to demonstrate an ef­ fect of age may be explained by excess variability. The issue is important, as the Eidelberg et ai. paper attempts to resolve disparate findings of an age re­ lationship in Fluorodopa uptake using different ROIs (Martin et aI., 1989; Sawle et aI., 1990). We have recently shown in a new data set that using total striatal ROIs reveals an aging effect in Fluorodopa uptake, while using small (8.8-mm­ diameter) ROIs does not (Vingerhoets et aI., 1994). These findings reconcile the differing conclusions of Martin et ai. (1989) (who used total striatal ROIs and found an age effect) and Sawle et ai. (1990) (who used small ROIs and did not). The difference between the methods does not relate just to the size of the ROIs; large ROIs measure the total striatal Fluorodopa uptake, while small ROIs measure the concentration of Fluorodopa uptake per milliliter of striatum. Eidelberg et ai. are confused by this point when they state that the total striatal ROI method is sensitive to the known age-related striatal atrophy (Murphy et aI., 1992). In fact, the opposite is true, because dopaminergic neurons make up a minimal part of the volume of the striatum. Any atrophy of the nondopaminergic elements would alter the con­ centration of Fluorodopa uptake but not the total uptake, which is therefore the true measure of ni­ grostriatal dopaminergic function. Eidelberg et ai. could have contributed to the dis­ cussion by applying the methods of both Martin et ai. and Sawle et ai. to the same data set. U nfortu­ nately they did not replicate the methods, and

  • Longitudinal Fluorodopa positron emission tomographic studies of the evolution of idiopathic parkinsonism
    Annals of neurology, 1994
    Co-Authors: Francois J G Vingerhoets, Barry J. Snow, Chong S. Lee, Michael Schulzer, Edwin Mak, Donald B. Calne
    Abstract:

    Previous estimates of the rate of progression of the nigral pathology underlying idiopathic parkinsonism (IP) have been derived mainly from pathological studies that have an inherent selection bias. Fluorodopa positron emission tomography (PET) is a reliable tool for assessing nigrostriatal dopaminergic function in vivo. We performed Fluorodopa PET on two occasions, 7 years apart, on 16 patients with IP (age at the time of the first scan, 51 +/- 14 yr [mean +/- SD]) and 10 normal controls (age, 54 +/- 16 yr). For the patients with IP, the average duration of symptoms from the time of diagnosis to the first scan was 4.5 years (range, 1-12 yr); their PET index (striatal-occipital)/occipital ratio, dropped by 1.7% per year, from 0.49 +/- 0.08 to 0.43 +/- 0.08 (p < 0.001). The normals' ratio decreased by 0.3% per year from 0.77 +/- 0.05 to 0.75 +/- 0.10 (p = 0.33). The ratios in the IP group progressed significantly faster than the controls (p = 0.036). The rate of decline in IP represents 7.8% per decade, expressed as a fraction of the normals' initial mean value at 54 years of age. These results also permit power analysis for the design of future studies assessing the effect of treatment on the underlying pathology in IP.

Juha O. Rinne - One of the best experts on this subject based on the ideXlab platform.

  • Reduced striatal dopamine synthesis capacity is associated with symptoms of depression in patients with de novo unmedicated Parkinson's disease.
    Journal of Parkinson's disease, 2013
    Co-Authors: Juho Joutsa, Juha O. Rinne, Olli Eskola, Valtteri Kaasinen
    Abstract:

    Abstract Previous studies have suggested that impaired striatal dopamine function might be independently related to depression in patients with Parkinson's disease (PD), but the results are not uniform. In this study, we investigated de novo unmedicated and medicated PD patients with more advanced disease using 18F-Fluorodopa-PET. In unmedicated de novo patients, but not in medicated patients, higher depression scores were associated with lower striatal 18F-Fluorodopa uptake. These results indicate that impaired striatal dopaminergic function in PD is related to depressive symptoms and that these effects can be observed in de novo patients without the confounding effects of advanced neurodegeneration and medications.

  • Increased medial orbitofrontal [18F]Fluorodopa uptake in Parkinsonian impulse control disorders.
    Movement disorders : official journal of the Movement Disorder Society, 2012
    Co-Authors: Juho Joutsa, Juha O. Rinne, Jarkko Johansson, Kirsti Martikainen, Solja Niemelä, Sarita Forsback, Valtteri Kaasinen
    Abstract:

    Background: Impulse control disorders (ICDs) occur frequently in PD patients. Methods: To investigate the possible involvement of the mesostriatal and mesolimbic monoaminergic function in ICDs associated with PD, we examined patients with (n = 10) and without (n = 10) ICDs using the brain [18F]Fluorodopa PET. Results: Patients with ICDs (e.g., pathological gambling, hypersexuality, and compulsive eating) showed up to 35% higher [18F]Fluorodopa uptake in the medial orbitofrontal cortex, compared to control patients, but no differences in the striatum. The results remained significant also after excluding subjects with comorbid psychiatric disorders. Conclusions: Increased monoaminergic activity in the medial orbitofrontal cortex might be associated with increased sensitivity for ICDs under dopamine-replacement therapy in PD. © 2012 Movement Disorder Society

  • positron emission tomography shows that impaired frontal lobe functioning in parkinson s disease is related to dopaminergic hypofunction in the caudate nucleus
    Neuroscience Letters, 2001
    Co-Authors: Anna Bruck, M Haaparanta, A. Laihinen, Olof Solin, Raija Portin, Arja Lindell, J Bergman, Juha O. Rinne
    Abstract:

    We examined the relation between the dopaminergic function and the cognitive performance of patients with Parkinson's disease (PD). The subject sample consisted of ten patients in the early course of PD and with no previous antiparkinsonian medication. The dopaminergic function of the caudate nucleus and the putamen was studied with [18F]Fluorodopa positron emission tomography, and the cognitive performance with a comprehensive battery of neuropsychological tests including tests sensitive to frontal lobe function. The decreased [18F]Fluorodopa uptake in the right caudate nucleus was found to be related to slow processing time, measured as the difference between the incongruent and the congruent subtests of the Stroop Test (r=−0.85, P=0.002), a similar trend was seen in the left caudate (r=−0.60, P=0.07). Similar correlation was not detected in the putamen. The present findings provide evidence that the decreased dopaminergic function in the right caudate nucleus is related to the impaired performance in tests sensitive to frontal lobe function in patients at an early stage of PD and with no antiparkinsonian medication.

  • Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]Fluorodopa positron emission tomographic study.
    Archives of neurology, 2000
    Co-Authors: Juha O. Rinne, H M Ruottinen, Merja Haaparanta, Jörgen Bergman, Raija Portin, Elina Nurmi, Olof Solin
    Abstract:

    Objective To investigate the role of the brain dopaminergic system in cognitive impairment in patients with Parkinson disease (PD). Design We studied 28 patients with PD and 16 age-matched healthy control subjects using [ 18 F]Fluorodopa (Fluorodopa F 18) positron emission tomography. Patients with PD showed a variable degree of cognitive impairment, which was assessed using the Mini-Mental State Examination and detailed neuropsychologic assessment, including tests sensitive for frontal lobe function. Results [ 18 F]Fluorodopa uptake was reduced in the putamen (to 36% of the control mean; P P P 18 F]Fluorodopa uptake values. The influx constant ( K i occ ) in the caudate nucleus had a negative association with performance in the attention-demanding Stroop interference task, especially with the interference time. The K i occ in the frontal cortex had a positive correlation with performance in the digit span (backwards), verbal fluency, and verbal immediate recall tests. Thus, the better the patient performed in tasks demanding immediate and working memory and executive strategies, the better the [ 18 F]Fluorodopa uptake in the frontal cortex. In the putamen, no significant correlation was seen between the K i occ value and any of the cognitive tests. The severity of the motor symptoms of PD and [ 18 F]Fluorodopa uptake showed a negative correlation in the putamen ( r = −0.38; P = .04), and in the caudate nucleus a similar trend was seen ( r = −0.36; P = .06). Conclusions Reduced [ 18 F]Fluorodopa uptake in PD in the caudate nucleus (and frontal cortex) is related to impairment in neuropsychologic tests measuring verbal fluency, working memory, and attentional functioning reflecting frontal lobe function. This indicates that dysfunction of the dopamine system has an impact on the cognitive impairment of patients with PD. However, our results do not exclude the possibility of more generalized cognitive impairment in PD, the pathophysiology of which is probably different and more generalized.

  • [18F]Fluorodopa PET shows striatal dopaminergic dysfunction in juvenile neuronal ceroid lipofuscinosis.
    Journal of neurology neurosurgery and psychiatry, 1997
    Co-Authors: H M Ruottinen, Juha O. Rinne, Merja Haaparanta, Jörgen Bergman, Olof Solin, Vesa Oikonen, I Järvelä, P Santavuori
    Abstract:

    OBJECTIVES: To investigate whether nigrostriatal dopaminergic hypofunction is related to the extrapyramidal symptoms in patients with juvenile neuronal ceroid lipofuscinosis (JNCL). METHODS: Nine patients with JNCL and seven healthy controls were studied using [18F]Fluorodopa PET. RESULTS: In the patients with JNCL [18F]Fluorodopa uptake (K[i][occ]) in the putamen was 60% of the control mean and the corresponding figure in the caudate nucleus was 79%. There was a weak correlation between putamen K(i)(occ) values and extrapyramidal symptoms of the patients evaluated by the motor part of the unified Parkinson9s disease rating scale (r = -0.57, P

Olof Solin - One of the best experts on this subject based on the ideXlab platform.

  • Personality Traits and Striatal Dopamine Synthesis Capacity in Healthy Subjects
    The American journal of psychiatry, 2003
    Co-Authors: Aki Laakso, Jörgen Bergman, Olof Solin, Esa Wallius, Jaana Kajander, Olli Eskola, Tuula Ilonen, Raimo K. R. Salokangas, Erkka Syvälahti, Jarmo Hietala
    Abstract:

    OBJECTIVE: Neuroimaging and genetic studies suggest that individual differences in the brain dopaminergic system contribute to the normal variability of human personality (e.g., social detachment and novelty seeking). The authors studied whether presynaptic dopamine function is also associated with personality traits. METHOD: Presynaptic dopamine synthesis capacity in the brain was measured with positron emission tomography and [18F]Fluorodopa in 33 healthy adults, and personality traits were assessed with the Karolinska Scales of Personality. Associations were studied by using a linear regression model controlling for the effects of age and gender on both variables. RESULTS: High scores on two of the anxiety-related personality scales, somatic anxiety and muscular tension, and on one aggressivity-related scale, irritability, were significantly associated with low [18F]Fluorodopa uptake in the caudate. No statistically significant associations were observed between [18F]Fluorodopa uptake and the detachmen...

  • positron emission tomography shows that impaired frontal lobe functioning in parkinson s disease is related to dopaminergic hypofunction in the caudate nucleus
    Neuroscience Letters, 2001
    Co-Authors: Anna Bruck, M Haaparanta, A. Laihinen, Olof Solin, Raija Portin, Arja Lindell, J Bergman, Juha O. Rinne
    Abstract:

    We examined the relation between the dopaminergic function and the cognitive performance of patients with Parkinson's disease (PD). The subject sample consisted of ten patients in the early course of PD and with no previous antiparkinsonian medication. The dopaminergic function of the caudate nucleus and the putamen was studied with [18F]Fluorodopa positron emission tomography, and the cognitive performance with a comprehensive battery of neuropsychological tests including tests sensitive to frontal lobe function. The decreased [18F]Fluorodopa uptake in the right caudate nucleus was found to be related to slow processing time, measured as the difference between the incongruent and the congruent subtests of the Stroop Test (r=−0.85, P=0.002), a similar trend was seen in the left caudate (r=−0.60, P=0.07). Similar correlation was not detected in the putamen. The present findings provide evidence that the decreased dopaminergic function in the right caudate nucleus is related to the impaired performance in tests sensitive to frontal lobe function in patients at an early stage of PD and with no antiparkinsonian medication.

  • Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]Fluorodopa positron emission tomographic study.
    Archives of neurology, 2000
    Co-Authors: Juha O. Rinne, H M Ruottinen, Merja Haaparanta, Jörgen Bergman, Raija Portin, Elina Nurmi, Olof Solin
    Abstract:

    Objective To investigate the role of the brain dopaminergic system in cognitive impairment in patients with Parkinson disease (PD). Design We studied 28 patients with PD and 16 age-matched healthy control subjects using [ 18 F]Fluorodopa (Fluorodopa F 18) positron emission tomography. Patients with PD showed a variable degree of cognitive impairment, which was assessed using the Mini-Mental State Examination and detailed neuropsychologic assessment, including tests sensitive for frontal lobe function. Results [ 18 F]Fluorodopa uptake was reduced in the putamen (to 36% of the control mean; P P P 18 F]Fluorodopa uptake values. The influx constant ( K i occ ) in the caudate nucleus had a negative association with performance in the attention-demanding Stroop interference task, especially with the interference time. The K i occ in the frontal cortex had a positive correlation with performance in the digit span (backwards), verbal fluency, and verbal immediate recall tests. Thus, the better the patient performed in tasks demanding immediate and working memory and executive strategies, the better the [ 18 F]Fluorodopa uptake in the frontal cortex. In the putamen, no significant correlation was seen between the K i occ value and any of the cognitive tests. The severity of the motor symptoms of PD and [ 18 F]Fluorodopa uptake showed a negative correlation in the putamen ( r = −0.38; P = .04), and in the caudate nucleus a similar trend was seen ( r = −0.36; P = .06). Conclusions Reduced [ 18 F]Fluorodopa uptake in PD in the caudate nucleus (and frontal cortex) is related to impairment in neuropsychologic tests measuring verbal fluency, working memory, and attentional functioning reflecting frontal lobe function. This indicates that dysfunction of the dopamine system has an impact on the cognitive impairment of patients with PD. However, our results do not exclude the possibility of more generalized cognitive impairment in PD, the pathophysiology of which is probably different and more generalized.

  • [18F]Fluorodopa PET shows striatal dopaminergic dysfunction in juvenile neuronal ceroid lipofuscinosis.
    Journal of neurology neurosurgery and psychiatry, 1997
    Co-Authors: H M Ruottinen, Juha O. Rinne, Merja Haaparanta, Jörgen Bergman, Olof Solin, Vesa Oikonen, I Järvelä, P Santavuori
    Abstract:

    OBJECTIVES: To investigate whether nigrostriatal dopaminergic hypofunction is related to the extrapyramidal symptoms in patients with juvenile neuronal ceroid lipofuscinosis (JNCL). METHODS: Nine patients with JNCL and seven healthy controls were studied using [18F]Fluorodopa PET. RESULTS: In the patients with JNCL [18F]Fluorodopa uptake (K[i][occ]) in the putamen was 60% of the control mean and the corresponding figure in the caudate nucleus was 79%. There was a weak correlation between putamen K(i)(occ) values and extrapyramidal symptoms of the patients evaluated by the motor part of the unified Parkinson9s disease rating scale (r = -0.57, P

  • Presynaptic dopamine function in striatum of neuroleptic-naive schizophrenic patients
    Lancet (London England), 1995
    Co-Authors: Jarmo Hietala, Merja Haaparanta, Ulla Ruotsalainen, Jörgen Bergman, Olof Solin, Erkka Syvälahti, Mikko Kuoppamäki, K. Vuorio, Viljo Räkköläinen, Olli Kirvelä
    Abstract:

    Presynaptic dopamine function (6-[18F]-Fluorodopa uptake) in the brains of seven neuroleptic-naive first-admission schizophrenic patients and eight healthy controls was studied with positron emission tomography. The Fluorodopa influx constant (Ki) in putamen was higher in the patients than in controls (average mean: 0.0149 vs 0.0129, p = 0.034). The changes in caudate were smaller but significantly lateralised to the left caudate. There was one catatonic schizophrenic patient in our sample. This patient had lower striatal Ki than any control. Alterations in striatal presynaptic dopamine function may constitute a part of disrupted neural circuits that predispose to schizophrenic psychosis.

John W Haycock - One of the best experts on this subject based on the ideXlab platform.

  • striatal 3 4 dihydroxyphenylalanine decarboxylase in aging disparity between postmortem and positron emission tomography studies
    Annals of Neurology, 1995
    Co-Authors: Stephen J Kish, Xiaohui H Zhong, Oleh Hornykiewicz, John W Haycock
    Abstract:

    Recent positron emission tomography (PET) studies using 3,4-[18F]fluorodihydroxyphenylalanine ([18F]Fluorodopa) have reported little or no decrement in dopaminergic function in human striatum (caudate and putamen) during aging. In contrast, previous postmortem studies have reported marked age-dependent decreases in the activity of dopa decarboxylase (DDC), a variable upon which the PET determinations depend. Using quantitative blot immunolabeling techniques, we measured DDC protein concentrations in postmortem striata of 28 neurologically normal subjects ranging in age from 17 to 103 years. We found a significant, albeit modest, age-dependent decrease in the concentration of DDC protein in caudate (r = -0.50, p 0.05), with mean values of the 87-year-old group being 27% (caudate) and 12% (putamen) lower than those of the 30-year-old group. The absence of a robust effect of aging upon striatal DDC protein is consistent with the [18F]Fluorodopa-PET studies that report either no change or only a relatively small decrease in striatal 18F accumulation during aging. To the extent that aging is associated with a substantial loss of striatal dopaminergic nerve terminals, the present results also suggest that DDC protein synthesis may be upregulated in those dopaminergic neurons that survive the aging process and, therefore, that striatal [18F]Fluorodopa uptake indices may provide an overestimate of the number of dopaminergic nerve terminals during physiological aging.

  • Striatal 3,4-dihydroxyphenylalanine decarboxylase in aging : disparity between postmortem and positron emission tomography studies ?
    Annals of neurology, 1995
    Co-Authors: Stephen J Kish, Xiaohui H Zhong, Oleh Hornykiewicz, John W Haycock
    Abstract:

    Recent positron emission tomography (PET) studies using 3,4-[18F]fluorodihydroxyphenylalanine ([18F]Fluorodopa) have reported little or no decrement in dopaminergic function in human striatum (caudate and putamen) during aging. In contrast, previous postmortem studies have reported marked age-dependent decreases in the activity of dopa decarboxylase (DDC), a variable upon which the PET determinations depend. Using quantitative blot immunolabeling techniques, we measured DDC protein concentrations in postmortem striata of 28 neurologically normal subjects ranging in age from 17 to 103 years. We found a significant, albeit modest, age-dependent decrease in the concentration of DDC protein in caudate (r = -0.50, p 0.05), with mean values of the 87-year-old group being 27% (caudate) and 12% (putamen) lower than those of the 30-year-old group. The absence of a robust effect of aging upon striatal DDC protein is consistent with the [18F]Fluorodopa-PET studies that report either no change or only a relatively small decrease in striatal 18F accumulation during aging. To the extent that aging is associated with a substantial loss of striatal dopaminergic nerve terminals, the present results also suggest that DDC protein synthesis may be upregulated in those dopaminergic neurons that survive the aging process and, therefore, that striatal [18F]Fluorodopa uptake indices may provide an overestimate of the number of dopaminergic nerve terminals during physiological aging.