Association of metabolic syndrome and change in Unified Parkinson\u27s Disease Rating Scale scores.

OBJECTIVE: To explore the association between metabolic syndrome and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT). METHODS: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome. RESULTS: Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p \u3c 0.0001), were more likely to be male (75.3% vs 57.0%; p \u3c 0.0001), and had a higher mean uric acid level (men 5.7 [1.3] vs 5.3 [1.1] mg/dL, women 4.9 [1.3] vs 3.9 [0.9] mg/dL, p \u3c 0.0001). Participants with metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS (p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS (p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores. CONCLUSIONS: Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding. CLINICALTRIALSGOV IDENTIFIER: NCT00449865

Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With Creatine.

OBJECTIVE: Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake. METHODS: Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from 45 movement disorders centers across the United States and Canada. A total of 1741 subjects with PD participated in the primary clinical study, and caffeine intake data were available for 1549 of these subjects. The association of caffeine intake with rate of progression of PD as measured by the change in the total Unified Parkinson Disease Rating Scale score and the interaction of this association with creatine intake were assessed. RESULTS: Caffeine intake was not associated with the rate of progression of PD in the main analysis, but higher caffeine intake was associated with significantly faster progression among subjects taking creatine. CONCLUSIONS: This is the largest and longest study conducted to date that addresses the association of caffeine with the rate of progression of PD. These data indicate a potentially deleterious interaction between caffeine and creatine with respect to the rate of progression of PD

Caffeine and Progression of Parkinson Disease

ObjectiveIncreased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake.MethodsData were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from 45 movement disorders centers across the United States and Canada. A total of 1741 subjects with PD participated in the primary clinical study, and caffeine intake data were available for 1549 of these subjects. The association of caffeine intake with rate of progression of PD as measured by the change in the total Unified Parkinson Disease Rating Scale score and the interaction of this association with creatine intake were assessed.ResultsCaffeine intake was not associated with the rate of progression of PD in the main analysis, but higher caffeine intake was associated with significantly faster progression among subjects taking creatine.ConclusionsThis is the largest and longest study conducted to date that addresses the association of caffeine with the rate of progression of PD. These data indicate a potentially deleterious interaction between caffeine and creatine with respect to the rate of progression of PD

Correlation of plasma concentrations of AEDs with their corresponding dried blood spot concentrations.

<p>Plasma concentrations of (<b>top left</b>) carbamazepine (<b>top right</b>) phenytoin and (<b>bottom</b>) valproic acid regressed against their dried blood spot concentrations using Deming regression. The broken line is the line of unity while the continuous line is the line of regression. The (<b>top left</b>) slope is 0.84 (95% CI, 0.76 to 1.00) and the intercept is 1.00 (95% CI, 0.04 to 1.97) for carbamazepine, (<b>top right</b>) slope is 1.61 (95% CI, 1.39 to 1.84) and the intercept is −1.14 (95% CI, −2.40 to 0.12) for phenytoin and (<b>bottom</b>) slope is 1.57 (95% CI, 1.33 to 1.81) and the intercept is 11.91 (95% CI, 5.73 to 18.09) for valproic acid.</p

Agreement between the plasma concentrations of carbamazepine and its dried blood spot concentration; and between the plasma concentrations of phenytoin and valproic acid and the theoretical plasma concentrations derived from their dried blood spot concentrations.

<p>Bland Altman plots for plasma concentrations of (<b>top</b>) carbamazepine, (<b>middle left</b>) phenytoin, K = 0.43, (<b>middle right</b>) phenytoin, K = 0.29, (<b>bottom</b><b>left</b>) valproic acid, K = 0.20 and (<b>bottom right</b>) valproic acid, K = 0.042. The broken lines represent the 95% CI (±1.96 SD) and the continuous line is the mean.</p

Characteristics of the people with epilepsy (PWE) grouped according to the type of antiepileptic drug.

<p>Total recruited PWE were 183. Only 169 were included in the analysis. The remaining 14 subjects were excluded due to missing plasma levels from hospital laboratory system. (Note: Some recruited PWE contributed to the levels of two AEDs).</p><p>Characteristics of the people with epilepsy (PWE) grouped according to the type of antiepileptic drug.</p

Tabulation of selective ion monitoring (SIM) attributes and the ions monitored for the respective analytes.

<p>Tabulation of selective ion monitoring (SIM) attributes and the ions monitored for the respective analytes.</p

Association of metabolic syndrome and change in Unified Parkinson's Disease Rating Scale scores

ObjectiveTo explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT).MethodsThis is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome.ResultsParticipants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p &lt; 0.0001), were more likely to be male (75.3% vs 57.0%; p &lt; 0.0001), and had a higher mean uric acid level (men 5.7 [1.3] vs 5.3 [1.1] mg/dL, women 4.9 [1.3] vs 3.9 [0.9] mg/dL, p &lt; 0.0001). Participants with metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS (p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS (p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores.ConclusionsPersons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding.Clinicaltrialsgov identifierNCT00449865

Association of metabolic syndrome and change in Unified Parkinson's Disease Rating Scale scores

To explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT). This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome. Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; < 0.0001), were more likely to be male (75.3% vs 57.0%; < 0.0001), and had a higher mean uric acid level (men 5.7 [1.3] vs 5.3 [1.1] mg/dL, women 4.9 [1.3] vs 3.9 [0.9] mg/dL, < 0.0001). Participants with metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS ( = 0.02) and 0.5- (0.2) unit increase in motor UPDRS ( = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores. Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding. NCT00449865

Identity of the plasma concentrations of phenytoin and valproic acid with the theoretical plasma concentrations derived from their dry blood spot concentrations.

<p>Plasma concentrations of (<b>top</b>) phenytoin and (<b>bottom</b>) valproic acid regressed against their theoretical plasma concentrations estimated from dried blood spot concentrations using Deming regression. [Theoretical plasma concentrations = Dried blood spot concentrations/1–Hct×(1–K)], where Hct is hematocrit and K is the RBC/plasma partition ratio. The broken line is the line of unity while the continuous line is the line of regression. The (<b>top left</b>) slope is 1.21 (95% CI, 1.04 to 1.38) and the intercept is −1.04 (95% CI, −2.32 to 0.24) for phenytoin with K = 0.43, (<b>top right</b>) slope is 1.11 (95% CI, 0.95 to 1.27) and the intercept is −1.00 (95% CI, −2.28 to 0.29) for phenytoin with K = 0.29, (<b>bottom left</b>) slope is 1.03 (95% CI, 0.87 to 1.20) and the intercept is 12.16 (95% CI, 5.95 to 18.37) for valproic acid with K = 0.2 and (<b>bottom right</b>) slope is 0.92 (95% CI, 0.77 to 1.07) and the intercept is 12.48 (95% CI, 6.15 to 18.81) for valproic acid with K = 0.042.</p