Association of body mass index and the depletion of nigrostriatal dopamine in Parkinson's disease.

Several antecedent studies had reported close relationship between low body weight and Parkinson's disease (PD). However, there have been few investigations about the role of body weight to nigrostriatal dopaminergic neurodegeneration. This study enrolled 398 de novo patients with PD whom underwent [18F] N-(3-Fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane positron emission tomography scan and body mass index (BMI) measurement. The relationships between BMI and dopamine transporter (DAT) activity were analyzed using linear regression analysis. A multivariate analysis adjusted for age, gender, disease duration, smoking status, coffee and tea consumption, and residence area revealed that BMI remained independently and significantly associated with DAT activity in all striatal subregions. Moreover, multiple logistic regression analyses showed that BMI was a significant predictor for the lowest quartile of DAT activity in the anterior putamen, ventral striatum, caudate nucleus, and total striatum. The present findings suggest that a low BMI might be closely associated with low density of nigrostriatal dopaminergic neurons in PD, which could support the evidence for the role of low body weight to PD-related pathologies.

Is normosmic Parkinson disease a unique clinical phenotype?

OBJECTIVE: Olfactory dysfunction is present in the majority of patients with early-stage Parkinson disease (PD) and can precede the onset of motor symptoms by many years. We performed this study to evaluate whether normosmic patients with PD had different clinical features compared to hyposmic patients. METHODS: We analyzed the data of 208 de novo patients with PD (mean age, 65.4 ± 9.7 years; range, 38-85 years; 104 men) who underwent both olfactory function tests and dopamine transporter (DAT) scans. RESULTS: Normosmic patients were significantly younger and had fewer motor deficits than hyposmic patients with PD. Striatal subregional DAT activities were comparable between the 2 groups, but intersubregional gradients were significantly higher in normosmic than hyposmic PD. A general linear model showed that normosmic patients with PD showed significantly fewer motor deficits after controlling the patient's age, sex, symptom duration, and DAT activity in the posterior putamen (p = 0.016). Levodopa-equivalent dose at approximately 2.5 years follow-up tended to be lower in normosmic than in hyposmic PD (p = 0.055). CONCLUSIONS: These results suggest that normosmic PD is a unique clinical phenotype with a more benign course, compared to hyposmic PD. Either less pathologic involvement in the olfactory system or a greater potential for olfactory neurogenesis in normosmic PD may contribute to this benign process compared to hyposmic PD.

Presynaptic dopamine depletion predicts levodopa-induced dyskinesia in de novo Parkinson disease.

OBJECTIVE: To investigate whether the magnitude of presynaptic dopamine depletion is a risk factor for the development of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) by quantitatively analyzing (18)F-FP-CIT PET data. METHODS: This retrospective cohort study enrolled a total of 127 drug-naive de novo patients with PD who completed (18)F-FP-CIT PET scanning at their initial evaluation. The patients visited our outpatient clinic every 3-6 months and had been followed for a minimum of 2 years since beginning dopaminergic medication. The predictive power of the quantitatively analyzed (18)F-FP-CIT uptake of striatal subregions and other clinical factors for the development of LID was evaluated using Cox proportional hazard models. RESULTS: During a mean follow-up period of 3.4 years, 35 patients with PD (27.6%) developed LID. Patients with LID showed less dopamine transporter (DAT) activity in the putamen than did those without LID. Multivariate Cox proportional hazard models revealed that the DAT uptakes of the anterior putamen (hazard ratio [HR] 0.530; p = 0.032), posterior putamen (HR 0.302; p = 0.024), and whole putamen (HR 0.386; p = 0.022) were significant predictors of the development of LID, whereas DAT activities in the caudate and ventral striatum were not significantly correlated with the development of LID. In addition, younger age at onset of PD and higher dose of levodopa were also significant predictors of the development of LID. CONCLUSIONS: The present results provide convincing evidence that presynaptic dopaminergic denervation in PD plays a crucial role in the development of LID.