Metabolic syndrome and genetic Parkinson's disease –the case of LRRK2 and GBA
Ofer Rotchild1, Anat Mirelman1, Tanya Gurevich3, Mali Gana-Weisz2, Orly Goldstein2, Meir Kestenbaum4, Jesse M Cedarbaum5, Avi Orr-Urtreger2, Nir Giladi1, Avner Thaler1
1Neurology, 2Genomic Research Laboratory for Neurodegeneration, Tel-Aviv Medical Center, 3Tel-Aviv Medical Center, 4Columbia University Medical Center, 5Coeruleus Clinical Sciences LLC
Objective:

To test whether metabolic syndrome (MS) influences Parkinson's disease (PD) severity and risk for future development of PD by assessing GBA and LRRK2 PD patients together with non-manifesting GBA and LRRK2 carriers (NMC) for the presence of components of the MS.  

Background:

MS is defined as the presence of three out of five components: abdominal obesity or elevated body mass index (BMI), elevated serum triglycerides, low serum HDL, high blood pressure and prediabetes (drug treatment for any of the last four conditions also fulfills the criteria). MS might have a role as a risk factor for PD however, it's influence on PD clinical phenotype, progression and risk for future development of PD is still unclear 

Design/Methods:
This cross-sectional observational study collected demographic information, blood pressure, laboratory test results, cognitive, motor, olfactory and affective information enabling the assessment of each component of the MS and the construction of the MDS prodromal probability score. Patients with PD and NMC were compared based on genetic status.
Results:

Five hundred sixty-two subjects participated in the study; 104 idiopathic PD patients, 40 LRRK2-PD, 70 GBA-PD patients, 196 healthy non-carriers, 55 LRRK2-NMC and 97 GBA-NMC. While PD groups did not differ in the number of metabolic components (p=0.101), LRRK2-PD had higher triglyceride levels (p=0.015) and higher rates of prediabetes (p=0.004) compared to iPD and GBA-PD.

NMC did not differ in the number of metabolic components (p=0.685) but LRRK2-NMC had higher triglyceride levels (p=0.014) compared to healthy non-carriers and GBA-NMC. NMC with probability rates for prodromal PD above 50% had higher frequencies of hypertriglyceridemia and prediabetes (p<0.005 and p=0.023 respectively) compared with those with lower probability scores.

Conclusions:

While there is no difference between genetic PD and NMC in the amount of MS components, elevated triglycerides and prediabetes were more frequent among LRRK2 carriers and might represent modifiable risk factors.