Nonlinear Progression of Parkinson Disease as Determined by Serial Positron Emission Tomographic Imaging of Striatal Fluorodopa F 18 Activity
University of Cologne, Köln, North Rhine-Westphalia, Germany JAMA Neurology
(Impact Factor: 7.42).
04/2005; 62(3):378-82. DOI: 10.1001/archneur.62.3.378
The investigation of disease progression provides important information on the dynamics of cell death in Parkinson disease (PD).
To determine the progression of dopaminergic impairment in PD with the use of positron emission tomography (PET).
Longitudinal prospective cohort study with a follow-up period of 64.5 +/- 22.6 months (mean +/- SD).
A consecutive sample of patients with PD (N = 31; age at symptom onset, 53.6 +/- 11.3 years) with a wide range of symptom duration and severity at the time of study entry.
Investigation by serial fluorodopa F 18 ([(18)F]fluorodopa) PET as a marker for striatal dopaminergic function.
Changes in caudate and putaminal [(18)F]fluorodopa influx constant (K(i)) values.
In patients with PD, the decline rate of putaminal [(18)F]fluorodopa K(i) correlated inversely with disease duration before study inclusion (r = -0.46, P = .01) and positively with baseline K(i) values (r = 0.44, P = .01), indicating a negative exponential loss of dopamine neurons. Annual disease progression rates ranged from 4.4% in the caudate nucleus to 6.3% in the putamen. A mean preclinical period of 5.6 +/- 3.2 years was calculated with symptom onset at a putaminal K(i) threshold of 69% from controls. Assuming nonlinear progression kinetics, the required sample size to prove neuroprotection with the use of [(18)F]fluorodopa PET was found to increase strongly with the preceding symptom duration of study subjects.
These data suggest that the neurodegenerative process in PD follows a negative exponential course and slows down with increasing symptom duration, contradicting the long-latency hypothesis of PD.
Available from: Marina Pizzi
- "These lines of evidence hint that synaptic í µí»¼-synuclein pathology could initiate and determine the onset of motor symptoms in PD. Indeed, clinical manifestations of the disease appear when dopamine levels in the striatum are reduced to 80% of normal levels, as measured by a decrease in [ 18 F] fluoro-DOPA PET binding, a consequence of dopamine neuron loss in substantia nigra   . Of note, this initial symptomatic phase is characterized by a significant worsening of putaminal presynaptic deficiency, with a marked reduction in dopamine presynaptic storage, transporter binding , and release  . "
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ABSTRACT: Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Its characteristic neuropathological features encompass the loss of dopaminergic neurons of the nigrostriatal system and the presence of Lewy bodies and Lewy neurites. These are intraneuronal and intraneuritic proteinaceous insoluble aggregates whose main constituent is the synaptic protein α-synuclein. Compelling lines of evidence indicate that mitochondrial dysfunction and α-synuclein synaptic deposition may play a primary role in the onset of this disorder. However, it is not yet clear which of these events may come first in the sequel of processes leading to neurodegeneration. Here, we reviewed data supporting either that α-synuclein synaptic deposition precedes and indirectly triggers mitochondrial damage or that mitochondrial deficits lead to neuronal dysfunction and α-synuclein synaptic accumulation. The present overview shows that it is still difficult to establish the exact temporal sequence and contribution of these events to PD.
Available from: Jiuquan Zhang
- "Furthermore, a hypothetical model of functional changes in the cerebellum accompanying the progression of PD has been described in their study . To be specific, pathological impairments should be more severe as disease progresses due to gradually development of the dopaminergic degeneration . The compensatory effect, by contrast, strengthens at a relatively early stage, but may diminish or eventually fail as pathological damages become more severe at the advanced stage . "
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ABSTRACT: Resting-state functional magnetic resonance imaging (RS-fMRI) has been considered for development as a biomarker and analytical tool for evaluation of Parkinson's disease (PD). Here we utilized analysis of the amplitude of low-frequency ﬂuctuations (ALFF) to determine changes in intrinsic neural oscillations in 72 patients with PD. Two different frequency bands (slow-5: 0.01-0.027Hz; slow-4: 0.027-0.073Hz) were analyzed. In the slow-5 band, PD patients compared with controls had increased ALFF values mainly in the caudate and several temporal regions, as well as decreased ALFF values in the cerebellum and the parieto-temporo-occipital cortex. Additionally, in the slow-4 band, PD patients relative to controls exhibited reduced ALFF value in the thalamus, cerebellum, and several occipital regions. Together, our data demonstrate that PD patients have widespread abnormal intrinsic neural oscillations in the corticostriatal network in line with the pathophysiology of PD, and further suggest the abnormalities are dependent on speciﬁc frequency bands. Thus, frequency domain analyses of resting state BOLD signals may provide a useful means to study the pathophysiology of PD and the physiology of the brain's dopaminergic pathways.
Available from: Brian Haas
- "PET can also be used as a highly sensitive measure to assess dopamine uptake and binding to the DAT. Accordingly, PET imaging, which assesses radiolabeled ligands for DAT, can be utilized to distinguish premotor PD [95,96]. Additionally, fMRI is another potential neuroimaging modality for use as a premotor biomarker for PD. "
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ABSTRACT: The second most serious neurodegenerative disease is Parkinson's disease (PD). Over the past several decades, a strong body of evidence suggests that PD can begin years before the hallmark clinical motor symptoms appear. Biomarkers for PD are urgently needed to differentiate between neurodegenerative disorders, screen novel therapeutics, and predict eventual clinical PD before the onset of symptoms. Some clinical evaluations and neuroimaging techniques have been developed in the last several years with some success in this area. Moreover, other strategies have been utilized to identify biochemical and genetic markers associated with PD leading to the examination of PD progression and pathogenesis in cerebrospinal fluid, blood, or saliva. Finally, interesting results are surfacing from preliminary studies using known PD-associated genetic mutations to assess potential premotor PD biomarkers. The current review highlights recent advances and underscores areas of potential advancement.
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