Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms that respond to dopaminergic therapy. However, there is increasing interest in nonmotor PD features such as hyposmia, sleep disorders, dementia, depression, and psychoses. We review neuroimaging studies in nonmotor symptoms of PD and the use of dopaminergic imaging to support screening of nonmotor symptoms for early PD. Neuroimaging data document nonmotor pathophysiologic involvement of systems beyond the nigrostriatal dopaminergic pathway. These neuroimaging studies support a broader view of PD with early involvement in time and wider involvement of monoamine and cortical systems that may provide targets for novel therapies for nonmotor symptoms.
[Show abstract][Hide abstract] ABSTRACT: A dopaminergic deficiency 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 deficiency 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 deficiency 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 deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
The Lancet Neurology 12/2009; 8(12):1128-39. DOI:10.1016/S1474-4422(09)70293-5 · 21.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reduction of 18F-fluorodeoxyglucose uptake in PET (hypometabolism) and grey matter volume in MRI (atrophy) are found in the cerebral cortex of patients with Parkinson’s disease (PD). This doctoral thesis studied the relationship between hypometabolism and atrophy in successive stages of cognitive decline in PD: cognitively normal, mild cognitive impairment (PD-MCI) and dementia (PDD); as well as the biochemical profile of hypometabolic and atrophic areas.
Z-score maps for atrophy and hypometabolism, obtained by comparing individual images to a data set of healthy control subjects, were compared using a direct voxel-based technique (paired Student’s t-test p<0.05 FDR corrected). Additionally, areas with hypometabolism and atrophy were biochemically characterized by proton magnetic resonance spectroscopy (MRS).
In PD-MCI patients hypometabolism exceeded atrophy in the angular gyrus, occipital, orbital and anterior frontal lobes. In PDD patients the hypometabolic areas observed in PD-MCI group were replaced by areas of atrophy, which were surrounded by extensive zones of hypometabolism. In both groups, areas where atrophy was more extended than hypometabolism were found in the precentral and supplementary motor areas in the temporal lobe and hippocampus. In the MRS study, the areas of hypometabolism and atrophy showed significant differences in resonance frequencies (1.27, 1.31, 1.62, 2.23 and 3.11 ppm) whose correlate is uncertain.
In conclusion, these findings suggest a gradient of severity in cortical changes associated with the development of cognitive impairment in PD, in which hypometabolism and atrophy represent consecutive stages of the same process. MRS technique may provide biochemical markers to be investigated in the near future.
09/2013, Degree: MD, PhD, Supervisor: José A. Obeso, María C. Rodríguez-Oroz
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