Heart Rate Variability in LRRK2 Parkinson’s Disease (S37.004)

OBJECTIVE: To determine whether heart rate variability (HRV) is reduced in LRRK2-associated Parkinson’s Disease (LRRK2-PD). BACKGROUND: Variability in the length of successive heart beat intervals derives from cardiac autonomic nervous innervation. HRV is reduced in idiopathic PD (iPD), reflecting cardiac autonomic dysfunction and associated synuclein pathology affecting the autonomic nervous system. HRV has been minimally studied in LRRK2-PD. DESIGN/METHODS: Five-minute resting EKGs were recorded on 10 subjects with PD with the LRRK2 G2019S mutation, 12 subjects with iPD, and 10 control subjects. HRV parameters were determined using Kubios software v.2.1. We compared HRV between groups using non-parametric tests and adjusted for age using logistic regression. RESULTS: iPD subjects were non-significantly older than LRRK2-PD and control subjects (median age: iPD 73.0, LRRK2-PD 60.5, control 62.5; all comparisons p>0.05), and had non-significantly longer PD duration (iPD 8.0 years, LRRK2-PD 5.2 years; p=0.4). As expected, HRV in iPD was lower than in controls, but unexpectedly, HRV in LRRK2-PD was greater than controls for most measures, and HRV in LRRK2-PD was substantially and significantly higher than in iPD. Significant differences in both time and frequency domain measures persisted after adjustment for age. Time domain median values in iPD, LRRK2-PD and controls: SDNN 13.0, 25.4, 18.3 (iPD vs LRRK2-PD adjusted p=0.046); RRtriindex 3.5, 7.2, 4.8 (iPD vs LRRK2-PD adjusted p=0.026). Frequency domain: LFms2 67.3, 301.9, 178.4 (iPD vs LRRK2-PD adjusted p=0.05); HFms2 46.1, 241.0, 53.6 (iPD vs LRRK2-PD adjusted p=0.05); total power 129.9, 638.6, 262.0 (iPD vs LRRK2-PD adjusted p=0.03). CONCLUSIONS: Unlike in iPD, HRV is not reduced in LRRK2-PD, suggesting a relative sparing of pathologic involvement of the autonomic innervation of the heart. This finding is consistent with several previous imaging studies of cardiac sympathetic innervation in LRRK2-PD, and provides evidence of possible pathogenetic differences between LRRK2-associated PD and idiopathic PD. Study Supported by: Michael J. Fox Foundation; Brin-Wojcicki Foundation Disclosure: Dr. Goldman has nothing to disclose. Dr. Schuele has nothing to disclose. Dr. Bhudhikanok has nothing to disclose. Dr. Cash has nothing to disclose. Dr. Korell has nothing to disclose. Dr. Amiri has nothing to disclose. Dr. Meng has nothing to disclose. Dr. Comyns has nothing to disclose. Dr. Guest has nothing to disclose. Dr. Rees has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Kausar has nothing to disclose. Dr. Sundarrajan has nothing to disclose. Dr. Drabant Conley has received personal compensation for activities with 23andMe Inc., as an employee. Dr. Drabant Conley holds stock and/or stock options in 23andMe Inc., which sponsored research in which Dr. Drabant Conley was involved as an investigator. Dr. Eriksson has received personal compensation for activities with 23andMe as an employee. Dr. Liang has received personal compensation for activities with Boehringer Ingelheim Pharmaceuticals Inc., GlaxoSmithKline Inc., Novartis, and Teva Neuroscience as a speaker, and with Chelsea as and advisor. Dr. Brandabur has nothing to disclose. Dr. Tetrud has received personal compensation for activities with GlaxoSmithKline Inc., Requip, Schwarz Pharma, Neupro, Valeant, Zelapar, Teva Neuroscience, and Azilect. Dr. Langston has nothing to disclose. Dr. Tanner has received personal compensation for activities with AbbVie and Adamas Pharmaceuticals as a scientific advisor.