Change In Levodopa Equivalent Dose Research Articles

Association between striatal amyloid deposition and motor prognosis in Parkinson's disease.

The co-occurrence of amyloid-β pathology in Parkinson's disease (PD) is common; however, the role of amyloid-β deposition in motor prognosis remains elusive. This study aimed to investigate the association between striatal amyloid deposition, motor complications and motor prognosis in patients with PD. Ninety-six patients with PD who underwent 18F florbetaben (FBB) positron emission tomography were retrospectively assessed. The ratio of the striatum to global (STG) FBB uptake was obtained for each individual, and patients were allotted into low and high STG groups according to the median value. The effect of STG group on regional amyloid deposition, the occurrence of motor complications and longitudinal change in levodopa equivalent dose (LED) requirement were investigated after controlling for age, sex, LED and disease duration at FBB scan. The high STG group was associated with lower cortical FBB uptake in the parietal, occipital and posterior cingulate cortices and higher striatal FBB uptake compared to the low STG group. Patients in the high STG group had a higher risk of developing wearing off and levodopa-induced dyskinesia than those in the low STG group, whereas the risk for freezing of gait was comparable between the two groups. The high STG group showed a more rapid increase in LED requirements over time than the low STG group. These findings suggest that relatively high striatal amyloid deposition is associated with poor motor outcomes in patients with PD.

Low skull bone density is associated with poor motor prognosis in women with Parkinson's disease.

Parkinson's disease (PD) and osteoporosis are degenerative diseases that have shared pathomechanisms. To investigate the associations of skull bone density with nigrostriatal dopaminergic degeneration and longitudinal motor prognosis in female patients with PD. We analyzed the data of 260 drug-naïve female PD patients aged ≥50 years old who were followed-up for ≥3 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging. We measured skull bone density as a surrogate marker for systemic bone loss by calculating the Hounsfield unit (HU) in computed tomography scans. A Cox proportional hazard model was built to compare the rates of levodopa-induced dyskinesia (LID) or wearing-off according to skull HU. Longitudinal changes in levodopa-equivalent dose (LED) during a 3-year follow-up were assessed using a linear mixed model. A lower skull HU was associated with lower baseline DAT availability in striatal subregions; however, this relationship was not significant after adjusting for age, disease duration, body mass index, and white matter hyperintensities. After adjusting for confounding factors, a lower skull HU was significantly associated with an increased risk of LID development (hazard ratio = 1.660 per 1 standard deviation decrease, p = 0.007) and wearing-off (hazard ratio = 1.613, p = 0.016) in younger (<67 years) but not in older patients. Furthermore, a lower skull HU was associated with a steeper increase in LED during follow-up in younger patients only (β = -21.99, p < 0.001). This study suggests that baseline skull bone density would be closely linked to motor prognosis in drug naïve women with PD.

Effects of statins on dopamine loss and prognosis in Parkinson's disease.

Statins are more widely used not only for the primary and secondary prevention of cardiovascular disease by blocking cholesterol biosynthesis but also for the potential neuroprotective agents during neurological disorders due to their pleiotropic effects. In this study, we investigate whether the previous use of statins affect baseline nigrostriatal dopamine loss at the time of diagnosis and longitudinal motor and cognitive outcomes in patients with Parkinson's disease. Five hundred drug-naïve patients with Parkinson's disease who underwent dopamine transporter imaging were classified into two groups according to the prior use of statins: patients with and without statin use. Multivariate linear regression was used to determine intergroup differences in dopamine transporter availability. We evaluated the longitudinal changes in levodopa-equivalent dose and dementia conversion between the groups using a linear mixed model and survival analysis, respectively. In addition, mediation analysis was applied to examine the effect of total cholesterol. Patients with Parkinson's disease treated with statins had a lower baseline dopamine transporter availability in the anterior (2.13 ± 0.55 versus 2.37 ± 0.67; P = 0.002), posterior (1.31 ± 0.43 versus 1.49 ± 0.54; P = 0.003) and ventral putamina (1.40 ± 0.39 versus 1.56 ± 0.47; P = 0.002) than that in matched patients with Parkinson's disease without statins. After adjusting for age at symptom onset, sex, disease duration and vascular risk factors, linear regression models showed that a previous treatment with statins remained significantly and independently associated with more severely decreased dopamine transporter availability in the anterior putamen (Beta = -0.140, P = 0.004), posterior putamen (Beta = -0.162, P = 0.001) and ventral putamen (Beta = -0.140, P = 0.004). A linear mixed model revealed that patients with Parkinson's disease being treated with statins had a faster longitudinal increase in levodopa-equivalent dose than those without. A survival analysis showed that the rate of dementia conversion was significantly higher in patients with Parkinson's disease with statins (hazard ratio, 2.019; 95% confidence interval, 1.108-3.678; P = 0.022) than those without. Mediation analyses revealed that the effect of statin treatment on baseline dopamine transporter availability and longitudinal outcome was not mediated by total cholesterol levels. This study suggests that statin use may have a detrimental effect on baseline nigrostriatal dopamine degeneration and long-term outcomes in patients with Parkinson's disease.

Gut microbiota-derived metabolite trimethylamine N-oxide as a biomarker in early Parkinson's disease

Abstract Objectives This study aimed to investigate the potential of using changes in the plasma levels of trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, as a biomarker in early Parkinson's disease (PD). Methods Plasma TMAO levels were measured in 85 patients with drug-naive early stage PD and 20 healthy controls. A linear mixed model was used to assess longitudinal changes in levodopa-equivalent dose (LED) during follow-up (>2 y) in three tertile PD groups according to plasma TMAO levels. Additionally, a Cox regression analysis was performed to assess the effect of plasma TMAO levels on dementia conversion. Results Plasma TMAO levels of patients with PD were lower than those of healthy controls. A linear mixed model demonstrated that patients with PD and lower levels of TMAO ( Conclusions The results demonstrate that lower baseline plasma TMAO levels are associated with faster increases in LED and tend to increase the risk for PD–dementia conversion, suggesting the prognostic implications of TMAO in early stage PD.

The effect of pramipexole extended release on the levodopa equivalent daily dose in Lebanese Parkinson diseased patients.

Objective:The objective of this study is to compute the potential benefit of Pramipexole ER on total levodopa equivalent dose (LED) and Unified Parkinson Disease Rating Score (UPDRS-III) compared to mono- or combined therapy of pramipexole IR and/or carbidopa/levodopa.Methods:This is a retrospective observational study conducted in a specialized PD (Parkinson Disease) and movement disease center in Lebanon between January and December 2017.Results:A total of 176 patient’s record was reviewed. Pramipexole ER showed a significant difference on the mean changes in LED and UPDRS-III score. After 13 weeks of initiating Pramipexole ER, the mean decrease in LED was -49.42 mg for all patients (p < 0.001, CI 95% [35.28-63.55]) and the mean decrease in UPDRS-III score for all patients was -6 points (P< 0.001).According to the subgroup analysis, patients aged 65 years and below, the change in mean total LED from baseline (350.80 mg) was a decrease of 63.19 mg with a p<0.001, CI 95% [42.07-84.31]. In patients aged more than 65 years and shifted to mono or combined pramipexole ER therapy, the change in mean total LED from baseline (559.25 mg) was a decrease of 34.67 mg with a p<0.001 CI 95% [16.16-53.18]. In addition the results showed that in patients having an UPDRS-III score of less than or equal to 33, the change in mean total LED from baseline (436.73 mg) was a decrease of 56.76 mg (p<0.001; CI 95% [41.32-72.20]). However, in patients having an UPDRS-III score of more than 33 the change in mean total LED from baseline (545.06 mg) was a decrease of 2.96 mg with a p value < 0.844 CI 95% [27.32-33.15].Conclusions:This study demonstrated the efficacy of Pramipexole ER on decreasing the total levodopa equivalent dose (LED).The role of health care professionals is to maintain the patient on the lowest effective levodopa equivalent daily dose and optimize the treatment therapy, thus decreasing the side effects that might arise from overdosing of antiparkinsonian drugs.

Levodopa-carbidopa intestinal gel: is the naso-jejunal phase a redundant convention?

Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment for Parkinson disease. Initiating therapy involves an initial naso-jejunal (NJ) titration phase. The NJ phase is prolonged with significant morbidity. The aim of this study is to assess the impact of proceeding without the NJ phase on resource utilisation and the outcomes of patients. Twenty-five patients were started on LCIG using the patients existing levodopa equivalent dose (LED). We recorded change in LED, length of hospital stay, readmission rates and use of outpatient services and clinical outcomes within 6 months. The median length of stay was 4.5 days. Patients had four outpatient clinic reviews and 2.5 community nurse contacts within 6 months. There was no significant change in daily LED on discharge (P = 0.56). There were significant improvements in all Unified Parkinson Disease Rating Scale subscores (P < 0.05), the Freezing of Gait scale (P < 0.01) and Parkinson Disease Quality Of Life 39 score (P < 0.01). Initiating LCIG without the NJ phase resulted in short admissions, a minimal outpatient burden and no significant requirement for dose titration while producing good clinical outcomes.