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Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease.

Abstract

PURPOSE

Cardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation.

METHODS

Short-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls.

RESULTS

Beat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls.

CONCLUSIONS

Increased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD.

Authors+Show Affiliations

Facultad de Biología, Universidad de La Habana, Calle 25 No. 455, Vedado, Plaza de la Revolución, 10400, La Habana, Cuba. carri@fbio.uh.cu.Edmond J Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, 399 Bathurst St, Toronto, ON, M5T 2S8, Canada.Edmond J Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, 399 Bathurst St, Toronto, ON, M5T 2S8, Canada.School of Electrical Engineering and Computing, University of Newcastle, University Dr, Callaghan, NSW, 2308, Australia.Department of Radiology, University of Calgary, 330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada.Department of Pathology, Stanford School of Medicine, 300 Pasteur Dr, R271, Stanford, CA, 94305, USA.Department of Neurology, University of California, 3333 California St, San Francisco, CA, 94118, USA.Departamento de Neurofisiología Clínica, Instituto de Neurología y Neurocirugía, Calle 29 No. 139, Vedado, Plaza de la Revolución, 10400, La Habana, Cuba.School of Medicine, Washington University, 660 S Euclid Ave, St. Louis, MO, 63110, USA.Edmond J Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, 399 Bathurst St, Toronto, ON, M5T 2S8, Canada.School of Community Health, Charles Sturt University, Elizabeth Mitchell Dr, Albury, NSW, 2640, Australia.Facultad de Biología, Universidad de La Habana, Calle 25 No. 455, Vedado, Plaza de la Revolución, 10400, La Habana, Cuba.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31444591

Citation

Carricarte Naranjo, Claudia, et al. "Increased Markers of Cardiac Vagal Activity in Leucine-rich Repeat Kinase 2-associated Parkinson's Disease." Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society, 2019.
Carricarte Naranjo C, Marras C, Visanji NP, et al. Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease. Clin Auton Res. 2019.
Carricarte Naranjo, C., Marras, C., Visanji, N. P., Cornforth, D. J., Sanchez-Rodriguez, L., Schüle, B., ... Machado, A. (2019). Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease. Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society, doi:10.1007/s10286-019-00632-w.
Carricarte Naranjo C, et al. Increased Markers of Cardiac Vagal Activity in Leucine-rich Repeat Kinase 2-associated Parkinson's Disease. Clin Auton Res. 2019 Aug 23; PubMed PMID: 31444591.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease. AU - Carricarte Naranjo,Claudia, AU - Marras,Connie, AU - Visanji,Naomi P, AU - Cornforth,David J, AU - Sanchez-Rodriguez,Lazaro, AU - Schüle,Birgitt, AU - Goldman,Samuel M, AU - Estévez,Mario, AU - Stein,Phyllis K, AU - Lang,Anthony E, AU - Jelinek,Herbert F, AU - Machado,Andrés, Y1 - 2019/08/23/ PY - 2019/04/03/received PY - 2019/08/10/accepted PY - 2019/8/25/pubmed PY - 2019/8/25/medline PY - 2019/8/25/entrez KW - Autonomic dysfunction KW - Deceleration capacity of heart rate KW - Heart rate variability KW - LRRK2 KW - Parkinson’s disease KW - Rényi entropy JF - Clinical autonomic research : official journal of the Clinical Autonomic Research Society JO - Clin. Auton. Res. N2 - PURPOSE: Cardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation. METHODS: Short-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls. RESULTS: Beat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls. CONCLUSIONS: Increased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD. SN - 1619-1560 UR - https://www.unboundmedicine.com/medline/citation/31444591/Increased_markers_of_cardiac_vagal_activity_in_leucine-rich_repeat_kinase_2-associated_Parkinson's_disease L2 - http://dx.doi.org/10.1007/s10286-019-00632-w DB - PRIME DP - Unbound Medicine ER -