We measured the concentrations of total (conjugated and unconjugated) monoamines (dopamine, DA; norepinephrine, NE) and monoamine metabolites (homovanillic acid, HVA; 3-methoxy-4-hydroxyphenyleneglycol, MHPG; 5-hydroxyindoleacetic acid, 5-HIAA) in the cerebrospinal fluid (CSF), using HPLC-ECD in 11 patients with Alzheimer's disease (AD) or senile dementia of the Alzheimer type (SDAT), 17 patients with vascular dementia of the Binswanger type (VDBT), and 15 controls. In AD/SDAT, there was a significant decrease in the DA concentration and a significant increase in the MHPG concentration. The average NE concentration was not altered, but significantly increased with the progression of intellectual disability. There were no significant changes in HVA and 5-HIAA concentrations. Patients with VDBT showed a significant increase in the DA concentration and a significant decrease in HVA and 5-HIAA concentrations. The DA concentrations increased significantly with the progression of dementia and ventricular enlargement. These results indicate that the noradrenergic and dopaminergic system in particular are altered in AD/SDAT, while the dopaminergic and serotonergic systems are mainly involved in VDBT.
We correlated monoamine concentrations in the cerebrospinal fluid from de novo (untreated) patients with Parkinson's disease with their clinical symptoms and therapeutic outcome after two years of L-dopa with/without other anti-parkinson medication. A significant correlation was found between the severity of some parkinsonian symptoms and the reduction in particular monoamines: Hoehn and Yahr's stage with dopamine, norepinephrine, and homovanillic acid: rigidity with dopamine; akinesia with dopamine and norepinephrine; freezing of gait with norepinephrine; and dementia with dopamine and homovanillic acid. Tremor had no correlations with the concentrations of the monoamines measured. Patients with dementia had a significantly increased level of epinephrine concentrations. Insufficient therapeutic responses of individual symptoms were associated with significantly decreased concentrations of particular monoamines before treatment: Hoehn and Yahr's stage with norepinephrine and epinephrine; akinesia with homovanillic acid and 5-hydroxyindoleacetic acid; and freezing of gait with dopamine, norepinephrine, homovanillic acid, and 5-hydroxyindoleacetic acid. These results suggest a significant correlation between the reduction in particular monoamines and the severity of some parkinsonian symptoms and their subsequent responses to L-dopa.
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