Abstract
In order toevaluate the influence of the metabolic syndrome (MS) (obesity, hypertension, elevated triglycerides, reduced levels of HDL cholesterol and glucose impairment) on the phenotype of LRRK2 and GBA Parkinson’s disease (PD), and on the prevalence of prodromal features among individuals at risk, we collected, laboratory test results, blood pressure, demographic, cognitive, motor, olfactory and affective information enabling the assessment of each component of MS and the construction of the MDS prodromal probability score. The number of metabolic components and their levels were compared between participants who were separated based on disease state and genetic status. One hundred and four idiopathic PD, 40 LRRK2-PD, 70 GBA-PD, 196 healthy non-carriers, 55 LRRK2-NMC and 97 GBA-NMC participated in this study. PD groups and non manifesting carriers (NMC) did not differ in the number of metabolic components (p = 0.101, p = 0.685, respectively). LRRK2-PD had higher levels of triglycerides (p = 0.015) and higher rates of prediabetes (p = 0.004), while LRRK2-NMC had higher triglyceride levels (p = 0.014). NMC with probability rates for prodromal PD above 50% had higher frequencies of hypertriglyceridemia and prediabetes (p < 0.005, p = 0.023 respectively). While elevated triglycerides and prediabetes were more frequent among LRRK2 carriers, MS does not seem to influence GBA and LRRK2-PD phenotype.
Highlights
In order toevaluate the influence of the metabolic syndrome (MS) on the phenotype of Leucine Rich Repeat Kinase 2 (LRRK2) and GBA Parkinson’s disease (PD), and on the prevalence of prodromal features among individuals at risk, we collected, laboratory test results, blood pressure, demographic, cognitive, motor, olfactory and affective information enabling the assessment of each component of MS and the construction of the MDS prodromal probability score
LRRK2-PD had higher University of Pennsylvania Smell Identification Test (UPSIT) scores (p = 0.008), higher rates of prediabetes (p = 0.004) and higher triglyceride levels (p = 0.015) which were correlated with disease duration (r = 0.332, p = 0.036) and Levodopa equivalent daily dose (LEDD) (r = 0.432, p < 0.001)
In the linear regression model, which was constructed to estimate the relationship between MS and its’ components and genotype, sex, age, REM sleep Behavior Disorder Questionnaire (RBDQ), UPDRS-III, Montreal Cognitive Assessment (MoCA), UPSIT, disease duration, LEDD and Non-Motor Symptoms Questionnaire (NMSQ), the number of MS components was associated with age and iPD status (Table 3)
Summary
In order toevaluate the influence of the metabolic syndrome (MS) (obesity, hypertension, elevated triglycerides, reduced levels of HDL cholesterol and glucose impairment) on the phenotype of LRRK2 and GBA Parkinson’s disease (PD), and on the prevalence of prodromal features among individuals at risk, we collected, laboratory test results, blood pressure, demographic, cognitive, motor, olfactory and affective information enabling the assessment of each component of MS and the construction of the MDS prodromal probability score. Among Jews from Ashkenazi (AJ) decent, mutations in the glucocerebrosidase (GBA) and Leucine Rich Repeat Kinase 2 (LRRK2) genes are present among more than 1/3 of the PD population[2] with specific phenotype for each mutation group[3,4] Penetrance estimations for these mutations are far from complete[5,6] due to genetic polymorphisms, environmental causes as well as inflammatory mechanisms[7,8]. The accumulation of ceramide impairs insulin action and promotes apoptosis potentially linking insulin resistance and inflammation[23] to date the relationship between these factors and PD have not been studied
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