Claudia Carricarte Naranjo, Connie Marras, Naomi P Visanji, David J Cornforth, Lazaro Sanchez-Rodriguez, Birgitt Schüle, Samuel M Goldman, Mario Estévez, Phyllis K Stein, Herbert F Jelinek, Anthony E Lang, Andrés Machado
{"title":"预测非帕金森LRRK2 G2019S突变携带者的运动和非运动损害的心跳特征","authors":"Claudia Carricarte Naranjo, Connie Marras, Naomi P Visanji, David J Cornforth, Lazaro Sanchez-Rodriguez, Birgitt Schüle, Samuel M Goldman, Mario Estévez, Phyllis K Stein, Herbert F Jelinek, Anthony E Lang, Andrés Machado","doi":"10.1007/s10286-024-01104-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Increased beat-to-beat heart rate variability (HRV) is a feature of patients with Parkinson's disease (PD) who carry the G2019S mutation in the LRRK2 gene (LRRK2-PD). Since LRRK2 mutations have incomplete penetrance, HRV changes preceding PD conversion would likely be observed only in a subset of LRRK2 non-manifesting carriers (NMC). We aimed to assess HRV in a subgroup of NMC with distinctive characteristics of LRRK2-PD, identified through clustering analysis.</p><p><strong>Methods: </strong>HRV measures derived from 300 normal heartbeat intervals extracted from the electrocardiograms of 25 NMC, 32 related non-carriers (RNC), 27 unrelated healthy controls, and 14 patients with LRRK2-PD were analyzed. Clinical symptoms were evaluated using questionnaires and scales, and three NMC subgroups were identified using a k-means cluster analysis on the basis of the deceleration capacity of heart rate (DC) and Rényi entropy. Standard and advanced HRV measures were compared using multiple regression analysis, controlling for age, sex, and mean heart rate.</p><p><strong>Results: </strong>Beat-to-beat HRV markers were significantly increased in a subgroup of seven NMC (NMC2, 28%) compared with RNC and controls. Increased irregularity and DC were also verified in the NMC2 compared with controls, and were typical traits in both the NMC2 and RNC. Overall, the HRV profile of NMC2 was comparable to that of patients with LRRK2-PD. NMC2 further exhibited greater motor and non-motor traits than the other NMC, RNC, and controls.</p><p><strong>Conclusions: </strong>Our results confirmed that HRV characteristics of LRRK2-PD are also found in a subset of NMC displaying clinical traits of LRRK2-PD. Further research is needed to clarify whether higher HRV represents a LRRK2-PD prodromal manifestation.</p>","PeriodicalId":10168,"journal":{"name":"Clinical Autonomic Research","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Heartbeat signature for predicting motor and non-motor involvement among nonparkinsonian LRRK2 G2019S mutation carriers.\",\"authors\":\"Claudia Carricarte Naranjo, Connie Marras, Naomi P Visanji, David J Cornforth, Lazaro Sanchez-Rodriguez, Birgitt Schüle, Samuel M Goldman, Mario Estévez, Phyllis K Stein, Herbert F Jelinek, Anthony E Lang, Andrés Machado\",\"doi\":\"10.1007/s10286-024-01104-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Increased beat-to-beat heart rate variability (HRV) is a feature of patients with Parkinson's disease (PD) who carry the G2019S mutation in the LRRK2 gene (LRRK2-PD). Since LRRK2 mutations have incomplete penetrance, HRV changes preceding PD conversion would likely be observed only in a subset of LRRK2 non-manifesting carriers (NMC). We aimed to assess HRV in a subgroup of NMC with distinctive characteristics of LRRK2-PD, identified through clustering analysis.</p><p><strong>Methods: </strong>HRV measures derived from 300 normal heartbeat intervals extracted from the electrocardiograms of 25 NMC, 32 related non-carriers (RNC), 27 unrelated healthy controls, and 14 patients with LRRK2-PD were analyzed. Clinical symptoms were evaluated using questionnaires and scales, and three NMC subgroups were identified using a k-means cluster analysis on the basis of the deceleration capacity of heart rate (DC) and Rényi entropy. Standard and advanced HRV measures were compared using multiple regression analysis, controlling for age, sex, and mean heart rate.</p><p><strong>Results: </strong>Beat-to-beat HRV markers were significantly increased in a subgroup of seven NMC (NMC2, 28%) compared with RNC and controls. Increased irregularity and DC were also verified in the NMC2 compared with controls, and were typical traits in both the NMC2 and RNC. Overall, the HRV profile of NMC2 was comparable to that of patients with LRRK2-PD. NMC2 further exhibited greater motor and non-motor traits than the other NMC, RNC, and controls.</p><p><strong>Conclusions: </strong>Our results confirmed that HRV characteristics of LRRK2-PD are also found in a subset of NMC displaying clinical traits of LRRK2-PD. Further research is needed to clarify whether higher HRV represents a LRRK2-PD prodromal manifestation.</p>\",\"PeriodicalId\":10168,\"journal\":{\"name\":\"Clinical Autonomic Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-02-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Autonomic Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10286-024-01104-6\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Autonomic Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10286-024-01104-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Heartbeat signature for predicting motor and non-motor involvement among nonparkinsonian LRRK2 G2019S mutation carriers.
Purpose: Increased beat-to-beat heart rate variability (HRV) is a feature of patients with Parkinson's disease (PD) who carry the G2019S mutation in the LRRK2 gene (LRRK2-PD). Since LRRK2 mutations have incomplete penetrance, HRV changes preceding PD conversion would likely be observed only in a subset of LRRK2 non-manifesting carriers (NMC). We aimed to assess HRV in a subgroup of NMC with distinctive characteristics of LRRK2-PD, identified through clustering analysis.
Methods: HRV measures derived from 300 normal heartbeat intervals extracted from the electrocardiograms of 25 NMC, 32 related non-carriers (RNC), 27 unrelated healthy controls, and 14 patients with LRRK2-PD were analyzed. Clinical symptoms were evaluated using questionnaires and scales, and three NMC subgroups were identified using a k-means cluster analysis on the basis of the deceleration capacity of heart rate (DC) and Rényi entropy. Standard and advanced HRV measures were compared using multiple regression analysis, controlling for age, sex, and mean heart rate.
Results: Beat-to-beat HRV markers were significantly increased in a subgroup of seven NMC (NMC2, 28%) compared with RNC and controls. Increased irregularity and DC were also verified in the NMC2 compared with controls, and were typical traits in both the NMC2 and RNC. Overall, the HRV profile of NMC2 was comparable to that of patients with LRRK2-PD. NMC2 further exhibited greater motor and non-motor traits than the other NMC, RNC, and controls.
Conclusions: Our results confirmed that HRV characteristics of LRRK2-PD are also found in a subset of NMC displaying clinical traits of LRRK2-PD. Further research is needed to clarify whether higher HRV represents a LRRK2-PD prodromal manifestation.
期刊介绍：
Clinical Autonomic Research aims to draw together and disseminate research work from various disciplines and specialties dealing with clinical problems resulting from autonomic dysfunction. Areas to be covered include: cardiovascular system, neurology, diabetes, endocrinology, urology, pain disorders, ophthalmology, gastroenterology, toxicology and clinical pharmacology, skin infectious diseases, renal disease.
This journal is an essential source of new information for everyone working in areas involving the autonomic nervous system. A major feature of Clinical Autonomic Research is its speed of publication coupled with the highest refereeing standards.
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