Influence of genetic, biological and pharmacological factors on levodopa dose in Parkinson's disease

2016 ◽  
Vol 17 (5) ◽  
pp. 481-488 ◽  
Author(s):  
Vivian Altmann ◽  
Artur F Schumacher-Schuh ◽  
Mariana Rieck ◽  
Sidia M Callegari-Jacques ◽  
Carlos RM Rieder ◽  
...  
2021 ◽  
Author(s):  
Jeremy Watts ◽  
Anahita Khojandi ◽  
Rama Vasudevan ◽  
Fatta B. Nahab ◽  
Ritesh Ramdhani

Abstract Parkinson’s disease (PD) medication treatment planning is generally based on subjective data through in-office, physicianpatient interactions. The Personal KinetiGraphTM (PKG) has shown promise in enabling objective, continuous remote health monitoring for Parkinson’s patients. In this proof-of-concept study, we propose to use objective sensor data from the PKG and apply machine learning to subtype patients based on levodopa regimens and response. We apply k-means clustering to a dataset of with-in-subject Parkinson’s medication changes—clinically assessed by the PKG and Hoehn & Yahr (H&Y) staging. A random forest classification model was then used to predict patients’ cluster allocation based on their respective PKG data and demographic information. Clinically relevant clusters were developed based on longitudinal dopaminergic regimens—partitioned by levodopa dose, administration frequency, and total levodopa equivalent daily dose—with the PKG increasing cluster granularity compared to the H&Y staging. A random forest classifier was able to accurately classify subjects of the two most demographically similar clusters with an accuracy of 87:9 ±1:3


2012 ◽  
pp. 1-5
Author(s):  
K.P. ROLAND ◽  
K.M.D. CORNETT ◽  
O. THEOU ◽  
J.M. JAKOBI ◽  
G.R. JONES

Background: Females with Parkinson’s disease (PD) are at greater risk of frailty than males. Little is known about how age and disease-related characteristics influence frailty in females with PD because frailty studies often exclude persons with underlying neurological pathologies. Objective: To determine age and diseaserelated characteristics that best explain physical frailty in community-dwelling females with and without PD. Design & Measurement: Correlation coefficients described relationships between PD-related characteristics and physical frailty phenotype criteria (Cardiovascular Health Study). Regression analysis identified associations between disease-related characteristics and frailty in non-PD and PD females. Setting: Community-dwelling. Participants: Females with mild to moderate PD (n = 17, mean age = 66 ± 8.5 years) and non-PD (n = 18, mean age = 72 ± 13.2 years) participated. Results: Daily carbidopa-levodopa dose best explained frailty in PD females (β = 0.5), whereas in non-PD females, age (β = 0.7) and comorbidity (β = 0.5) were most associated with frailty. Conclusions: Dopaminergic medication explained frailty in PD and not measures of disease progression (i.e. severity, duration). In females without PD age-related accumulation of comorbidities resulted in greater risk of frailty. This indicates dopaminergic management of PD symptoms may better reflect frailty in females with PD than disease severity or duration. These data suggest the influence of underlying frailty should be considered when managing neurological conditions. Understanding how frailty concurrently exists with PD and how these conditions progress within the aging female will facilitate future care management.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Kaitlyn P. Roland ◽  
Kayla M. D. Cornett ◽  
Olga Theou ◽  
Jennifer M. Jakobi ◽  
Gareth R. Jones

Females with Parkinson’s disease (PD) are vulnerable to frailty. PD eventually leads to decreased physical activity, an indicator of frailty. We speculate PD results in frailty through reduced physical activity.Objective. Determine the contribution of physical activity on frailty in PD (n=15, 65 ± 9 years) and non-PD (n=15, 73 ± 14 years) females.Methods. Frailty phenotype (nonfrail/prefrail/frail) was categorized and 8 hours of physical activity was measured using accelerometer, global positioning system, and self-report. Two-way ANCOVA (age as covariate) was used to compare physical activity between disease and frailty phenotypes. Spearman correlation assessed relationships, and linear regression determined associations with frailty.Results. Nonfrail recorded more physical activity (intensity, counts, self-report) compared with frail. Self-reported physical activity was greater in PD than non-PD. In non-PD, step counts, light physical activity time, sedentary time, and self-reported physical activity were related to frailty (R=0.91). In PD, only carbidopa-levodopa dose was related to frailty (r=0.61).Conclusion. Physical activity influences frailty in females without PD. In PD females, disease management may be a better indicator of frailty than physical activity. Further investigation into how PD associated factors contribute to frailty is warranted.


2019 ◽  
Vol 160 (17) ◽  
pp. 662-669 ◽  
Author(s):  
József Attila Szász ◽  
Szabolcs Szatmári ◽  
Viorelia Constantin ◽  
István Mihály ◽  
Attila Rácz ◽  
...  

Abstract: Introduction: The motor and non-motor complications of Parkinson’s disease impair the patients’ quality of life and limit therapeutical options. There are no clear criteria for ‘advanced’ Parkinson’s disease or for the optimal moment for invasive therapies. There is little evidence regarding the upper limits of levodopa doses, and how these may be influenced by the availability of device-aided therapies. Aim: To analyze substitution therapy in patients with advanced Parkinson’s disease. Method: In our retrospective study, we analyzed the data from all patients with advanced Parkinson’s disease hospitalized between 1st June 2011 and 31st May 2017, receiving combined levodopa treatment at least 4×/day, reporting a minimum of 2 hours off periods, with or without dyskinesia. We analyzed levodopa therapy for patients who were recommended either device-aided or conservative therapy. Results: Out of 311 patients with advanced Parkinson’s disease, for 125 we proposed device-aided therapies whereas in 42 patients we increased the levodopa dose. The average levodopa doses and the administration rate were higher for the 107 patients tested for levodopa-carbidopa intestinal gel. Disease duration, mean levodopa doses and frequency of dosing were all higher in patients proposed for device-aided therapies versus patients with continued conservative treatment. Conclusion: Our patients were on lower levodopa doses (compared to literature), but the combinations were used more often. Device-aided therapies should be considered in patients with severe motor complications who receive at least 750–1000 mg levodopa daily, divided minimum 5×/day. These patients need to be tested in specialized centers by multidisciplinary teams in order to make the best decision for further action. Orv Hetil. 2019; 160(17): 662–669.


2003 ◽  
Vol 18 (5) ◽  
pp. 573-578 ◽  
Author(s):  
Tomoyuki Uchiyama ◽  
Ryuji Sakakibara ◽  
Takamichi Hattori ◽  
Tomonori Yamanishi

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. P06.091-P06.091 ◽  
Author(s):  
T. Mera ◽  
M. Burack ◽  
F. Bonsignore ◽  
J. Giuffrida

2020 ◽  
pp. 089198872096425
Author(s):  
Diego Santos-García ◽  
E. Suárez Castro ◽  
T. de Deus Fonticoba ◽  
M. J. Feal Panceiras ◽  
J. G. Muñoz Enriquez ◽  
...  

Introduction: The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients. Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson’s disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems. Results: The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015–1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009–1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments. Conclusion: Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.


2020 ◽  
Vol 10 (4) ◽  
pp. 1657-1673
Author(s):  
Aliyah Glover ◽  
Lakshmi Pillai ◽  
Shannon Doerhoff ◽  
Tuhin Virmani

Background: Freezing of gait (FOG) is a debilitating feature of Parkinson’s disease (PD) for which treatments are limited. To develop neuroprotective strategies, determining whether disease progression is different in phenotypic variants of PD is essential. Objective: To determine if freezers have a faster decline in spatiotemporal gait parameters. Methods: Subjects were enrolled in a longitudinal study and assessed every 3– 6 months. Continuous gait in the levodopa ON-state was collected using a gait mat (Protokinetics). The slope of change/year in spatiotemporal gait parameters was calculated. Results: 26 freezers, 31 non-freezers, and 25 controls completed an average of 6 visits over 28 months. Freezers had a faster decline in mean stride-length, stride-velocity, swing-%, single-support-%, and variability in single-support-% compared to non-freezers (p < 0.05). Gait decline was not correlated with initial levodopa dose, duration of levodopa therapy, change in levodopa dose or change in Montreal Cognitive Assessment scores (p > 0.25). Gait progression parameters were required to obtain 95% accuracy in categorizing freezers and non-freezers groups in a forward step-wise binary regression model. Change in mean stride-length, mean stride-width, and swing-% variability along with initial foot-length variability, mean swing-% and apathy scores were significant variables in the model. Conclusion: Freezers had a faster temporal decline in objectively quantified gait, and inclusion of longitudinal gait changes in a binary regression model greatly increased categorization accuracy. Levodopa dosing, cognitive decline and disease severity were not significant in our model. Early detection of this differential decline may help define freezing prone groups for testing putative treatments.


Sign in / Sign up

Export Citation Format

Share Document