Prevalence and Impact of Orthostatic Hypotension in Parkinson's Disease: A Systematic Review and Meta-Analysis

Prevalence and Impact of Orthostatic Hypotension in Parkinson's Disease: A Systematic Review and Meta-Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prevalence and Impact of Orthostatic Hypotension in Parkinson's Disease: A Systematic Review and Meta-Analysis Hui Wang, Chi Zhang, Dongxun Xu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6061276/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Jul, 2025 Read the published version in Clinical Autonomic Research → Version 1 posted 4 You are reading this latest preprint version Abstract Objective: Parkinson’s disease (PD) is frequently associated with orthostatic hypotension (OH). Research on the prevalence of OH in PD and its effects on patients has produced inconsistent findings. Methods: A systematic review and meta-analysis were performed by searching for studies related to PD and OH in the PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled as necessary to calculate the prevalence of OH in PD patients, along with odds ratios (OR), weighted mean differences (WMD), or standardized mean difference (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I²statistic. Results: The prevalence of OH in patients with PD was found to be 33.1% (95% CI, 29.3%-37%) in a pooled sample of 7,748 subjects. Patients with PD and OH were significantly older at the time of examination (WMD 2.92 years) and had a longer disease duration (WMD 0.71 years) compared to those without OH. There was no significant difference in the distribution of sex, or in the scores of Unified Parkinson's Disease Rating Scale (UPDRS) parts I and II, as well as the total scores among Parkinson's disease patients with or without OH. Additionally, PD patients with OH exhibited significantly higher UPDRS scores across part 3 section scores (SMD 0.41, 95% CI 0.23 to 0.59). Conclusion: The prevalence of OH in PD is 33.1%. Patients with PD and OH are generally older at examination, have a longer disease duration, and display more severe disease manifestations compared to those without OH. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Parkinson’s disease (PD) represents a prevalent neurodegenerative condition, primarily identified by motor manifestations like bradykinesia, rigidity, tremor, and postural instability[6]. Furthermore, non-motor symptoms considerably diminish the quality of life for individuals with PD, which include issues such as constipation, abnormal urination, sexual dysfunction, excessive sweating, and orthostatic hypotension (OH) [7]. OH is recognized as one of the most common forms of cardiovascular autonomic dysfunction in PD, even in its initial stages, with reported prevalence rates between 4.6% and 84.7% [13-66]. It is characterized by a drop of at least 20 mmHg in systolic blood pressure or a minimum of 10 mmHg in diastolic blood pressure within three minutes of assuming an upright position or undergoing a head-up tilt[1]. The condition can result in symptoms like weakness, dizziness, neck pain, falls, and syncope, which underscores its clinical significance [10]. Recent investigations have highlighted the role of several factors, including age, the severity of the disease, medication use, and hypertension, as contributors to the risk of developing OH[10]. Previous studies proposed that PD can be divided into two subtypes: the body-first subtype, where pathological α-synuclein originates from the peripheral nervous system (PNS), and the brain-first subtype, where α-synuclein begins in the central nervous system (CNS)[73,74]. Earlier studies indicate that OH might serve as a clinical marker for the “body-first” subtype of PD, marked by initial autonomic dysfunction, where the heart and peripheral nerves are affected before progression to the central nervous system[75]. Patients with this subtype may experience a more rapid progression towards multisystem involvement[75]. Additionally, PD accompanied by OH is frequently linked to more severe symptoms, such as rapid eye movement sleep behavior disorder (RBD) and cognitive decline[76,77]. Prompt identification of OH is vital, as its occurrence may suggest early indications of multisystem neurologic dysfunction. OH is prevalent in multiple system atrophy (MSA), and MSA patients experiencing OH exhibit more severe disease symptoms than those without OH [67]. The nonmotor symptoms of PD are often overlooked in comparison to the motor symptoms. However, many nonmotor symptoms, such as OH, may impact a patient's disease progression and quality of life. Therefore, the prevalence of OH in PD and its potential impact on the disease itself equally deserving of our attention. In recent years, there has been a notable increase in studies investigating the effects of OH on disease severity in PD patients compared to earlier research; however, these studies have produced varying results. Some studies indicate that PD patients with OH tend to be older, have a longer disease duration, and exhibit more severe symptoms than their counterparts without OH [16,33]. Conversely, other studies report no significant differences in age, disease duration, or severity between PD patients with and without OH [36,40,45,49]. This reminds us that integrating previous studies for meta-analysis is necessary. This study presents a comprehensive systematic review and meta-analysis of all published articles concerning the prevalence of OH in PD and its effects on the disease. Methods Searching strategy This meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO, No. CRD42025636764) and was conducted in accordance with the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)(5). The Cochrane Collaboration definition for systematic review and meta-analysis was strictly followed. Two authors (H. Wang and C. Zhang) independently searched Medline via PubMed, Web of Science, Embase via embase.com, and Cochrane databases for original published studies on the clinical manifestations of PD patients with or without OH. Inclusion criteria were studies published in English between January 2000 and December 2024.The search string was as follows: ("Hypotension, Orthostatic" OR "Hypotension, Postural" OR "Postural Hypotension" OR "Orthostatic Hypotension") AND ("Idiopathic Parkinson's Disease" OR "Lewy Body Parkinson's Disease" OR "Parkinson Disease" OR "Parkinson's Disease, Idiopathic" OR "Parkinson's Disease, Lewy Body" OR "Paralysis Agitans" OR "Parkinson's Disease" OR "Idiopathic Parkinson Disease" OR "Lewy Body Parkinson Disease" OR "Primary Parkinsonism" OR "Parkinsonism, Primary" OR "Parkinson Disease, Idiopathic" OR "Parkinson Disease"). Study selection criteria Articles were initially screened based on their titles and abstracts, with full text consulted when necessary. Patients were diagnosed with OH according to a fall of ≥20 mmHg systolic or ≥10 mmHg diastolic blood pressure upon 1–3 min of active standing or head up tilt [1]. Inclusion criteria were as follows: (1) studies must be cross-sectional, case-control, or cohort designs published as original research; (2) only studies that investigated the presence of orthostatic hypotension (OH) in more than one underlying disorder were included; (3) the primary outcome of interest was OH; (4) studies needed to provide the prevalence of OH in PD or offer sufficient data to calculate these results; and (5) adequate data must be available to assess differences in the incidence or severity of motor symptoms associated with PD. Exclusion criteria were: (1) reviews, editorials, letters, conference abstracts, or case reports; (2) studies focusing exclusively on OH characteristics, pathogenic mechanisms, or PD management related to OH; (3) comparisons between PD and other synucleinopathies; (4) studies with insufficient data for meta-analysis; (5) non-English articles; and (6) studies not involving animal subjects. Discrepancies regarding article inclusion were resolved by a third author, D. Xu. Data extraction and study quality assessment The data extracted from the original articles included the surname of the first author, publication year, country, sample size, method of OH assessment, prevalence of OH, mean age of patients, sex, disease duration, and score on the Unified Parkinson’s Disease Rating Scale (UPDRS). For longitudinal studies, only baseline data were extracted. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for case-control and cohort studies, along with the Agency for Healthcare Research and Quality (AHRQ) guidelines for cross-sectional studies [2, 3]. Any discrepancies were resolved through consensus among all authors. Statistical analysis The STATA software version 16.0 was used for statistical analysis. Odds ratio (OR), weighted mean difference (WMD), or standardized mean difference (SMD) with 95% confidence intervals (95% CI) were used to report pooled results on dichotomous and continuous variables. A pvalue equal to or less than 0.05 was considered statistically significant. Due to the assessment of some included literature using the UPDRS scale while others utilized the MDS-UPDRS scale, which exhibit significant differences in scoring specifications, we conducted our analysis using the Standardized Mean Difference (SMD).The primary outcome measure was frequency of OH in PD as reported in prevalence (%). The pooled prevalence of RBD and 95% confidence intervals were obtained by using a DerSimonian-Laird random-effects model with double arcsine transformation (4). Meta-regression analyses were used to assess whether disease duration affects the UPDRS scores in PD with OH patients. The heterogeneity across studies was evaluated using Cochrane’s I 2 values. I 2 > 75% was defined as high heterogeneity, 50% < I 2 < 75% as moderate heterogeneity, 25% < I 2 < 50% as low heterogeneity, and I 2 < 25% as homogeneity. We used a fixed-effects model to meta-analyze data showing homogeneity and low heterogeneity, and a random-effects model to analyze data classified as moderate or high heterogeneity. A sensitivity analysis was performed to detect potential sources of heterogeneity. We used the one by one elimination method on STATA to perform sensitivity analyses to detect potential sources of heterogeneity, and a funnel plot and Begg’s test was created to detect publication biases. Result The literature search identified 3,718 potentially relevant articles (Fig. 1). After the removal of duplicates, 1,326 records were reviewed, resulting in the exclusion of 1,213 during the title and abstract screening phase. Subsequently, 113 full-text articles were assessed for eligibility, of which 59 were excluded for various reasons: 16 were reviews, 6 were studies focused on treatment, 7 were unrelated to PD, 18 were unrelated to OH, 5 were letters, 1 was a case report, and 6 had insufficient data. Ultimately, 54 articles were included in our review, encompassing a total of 7,748 PD patients. Among these, 29 original studies were conducted in Asia, 9 in America, 14 in Europe, 1 in Africa, and 1 across multiple continents. A meta-analysis was performed for all PD patients, defined by the prevalence of OH, age, sex, disease duration, and scores on the UPDRS. Prevalence of OH As demonstrated in Table 1 and Figure 2.1, the summary prevalence of OH in PD, including the results of the present study, was found to be 33.1% (95% CI, 29.3%-37%) from a pooled sample of 7,698 subjects. This study exhibited high heterogeneity (I² = 93.2%). Furthermore, there was no evidence of publication bias, as indicated by a non-significant result in Begg's test (Supplementary Figure 1.1.A). Sensitivity analysis confirmed that the results remained unchanged (Supplementary Figure 1.1.B). As shown in Table 1 and Figure 2.2, the summary prevalence of OH in PD was 31.2% (95% CI, 23.9%-38.5%) in Europe and America, which is comparable to the prevalence in Asia, reported at 34% (95% CI, 30.2%-37.8%). Again, there was no evidence of publication bias, as Begg's test yielded non-significant results (Supplementary Figures 1.2.A and 1.3.A). Sensitivity analysis also showed consistent results (Supplementary Figures 1.2.B and 1.3.B). Differences in age, gender, and disease duration between PD patients with or without OH Subgroup analysis based on age included 3,914 patients (Table 2). PD patients with OH were significantly older at the time of examination compared to those without OH (WMD 2.92 years, 95% CI 1.81 to 4.04; I² = 65.6%; Fig. 3). There was no evidence of publication bias, as Begg's test yielded a non-significant result (Supplementary Fig. 2.1). The heterogeneity of this study was moderate (I² = 65.6%). Sensitivity analysis indicated that the results remained unchanged (Supplementary Fig. 2.2). A total of 3,914 patients with PD from 24 studies were included in the analysis by sex (Table 2). No significant difference in sex distribution was observed between PD patients with or without OH (Fig. 4). Our study demonstrated homogeneity (I² = 0%). Begg's test did not reveal significant publication bias (Supplementary Fig. 3). A meta-analysis of the disease duration in 3,014 patients with PD from 22 studies indicated that the disease duration in PD patients with OH was significantly longer than in those without OH (WMD 0.71, 95% CI 0.29 to 1.14; Fig. 5). Begg's test did not show significant publication bias (Supplementary Fig. 4.1). The heterogeneity of this study was moderate (I² = 71.5%). Sensitivity analysis confirmed that the results remained unchanged (Supplementary Fig. 4.2). Differences in UPDRS scores between PD patients with or without OH A total of 989 patients with PD from 6 studies were included in the analysis of UPDRS part I section scores. The results indicated that there was no significant difference in the distribution of UPDRS part I section scores among Parkinson's disease patients with or without OH ( Fig. 6.A). The heterogeneity of this study was low (I² =26%). Begg's test did not reveal significant publication bias (Supplementary Fig. 5.1.1). Similarly, a total of 989 patients with PD from 6 studies were included in the analysis of UPDRS part II section scores. The results indicated that there was no significant difference in the distribution of UPDRS part II section scores among Parkinson's disease patients with or without OH ( Fig. 6.B). The heterogeneity of this study was homogeneity (I² = 16.6%). Begg's test did not indicate significant publication bias (Supplementary Fig. 5.2.1). A total of 1990 patients with PD from 13 studies were included in the analysis of UPDRS Part III section scores. The results indicated that the UPDRS Part III section scores in PD patients with OH were significantly higher than those in PD patients without OH (SMD 0.41, 95% CI 0.23 to 0.59; Fig. 6.C). Begg's test did not reveal significant publication bias (Supplementary Fig. 5.3.1). The heterogeneity of this study was moderate (I² = 64.7%). Sensitivity analysis yielded consistent results (Supplementary Fig. 5.3.2). We conducted meta-regression analyses to evaluate whether disease duration influences the UPDRS part III section scores in PD with OH patients; the findings indicated that disease duration does not affect the statistical results (R 2 =65.03%, P = 0.287; Fig. 7). Additionally, a total of 848 patients with PD from 5 studies were included in the analysis of total UPDRS scores. The results indicated that there was no significant difference in the distribution of total UPDRS scores among Parkinson's disease patients with or without OH (Fig. 6.D). Begg's test did not indicate significant publication bias (Supplementary Fig. 5.4.1). The heterogeneity of this study was low (I² = 41.5%). Discussion Previous studies have demonstrated a wide range of prevalence rates for OH in PD, with estimates varying from 4.6% to 84.7% (see Table 1). The meta-analysis conducted in this study revealed a notable prevalence rate of OH among patients with PD, recorded at 33.1%, with a 95% confidence interval ranging from 29.1% to 36.3% (Fig. 2.1). This finding is slightly higher than the results of earlier meta-analyses, which reported a prevalence rate of 27.7% [68]. To mitigate the potential impact of geographic and cultural factors on the observed overall prevalence of OH, we performed separate meta-analyses for the prevalence of OH in patients with PD across Europe, the Americas, and Asia. The results indicated that the summary prevalence of OH in PD was comparable between Europe and the Americas (31.2%) and Asia (34%). Previous studies have yielded inconsistent findings regarding the variability of age, age of disease duration, and UPDRS scores in patients with PD, both with and without OH. Some studies indicate that PD patients with OH tend to be older, have a longer disease duration, and exhibit more severe symptoms compared to those without OH [16, 33]. However, other studies have not supported these conclusions [36, 40, 45, 49]. To address this disparity, we conducted a meta-analysis encompassing all relevant studies on the impact of OH on PD, thereby increasing the sample size for more robust conclusions. Our analysis revealed that PD patients with OH were significantly older than their counterparts without OH at the time of examination (Fig. 3). Additionally, the disease duration for PD patients with OH was markedly longer than that for those without OH (Fig. 5), and PD patients with OH exhibited significantly higher UPDRS scores across parts 3 section (Fig. 6). These findings indicate that PD patients with OH experience more severe motor symptoms (refer to UPDRS-III section for variability) compared to PD patients without OH. However, our findings indicate that PD patients with OH tend to have a longer disease duration, which may result in the manifestation of more severe disease-related symptoms. Consequently, We conducted meta-regression analyses to evaluate whether disease duration influences the UPDRS scores in PD with OH patients. The results revealed that disease duration did not significantly affect the statistical outcomes of the differences in UPDRS-III scores for PD with OH patients. This finding suggests that PD patients with OH may have a longer disease duration, and OH may intensify motor symptoms. The pathological basis of PD primarily involves the degeneration and necrosis of nigrostriatal dopamine neurons, attributed to the formation and aggregation of Lewy bodies [69,70]. In addition to the nigrostriatal system, similar pathological changes can be observed in other regions of the central nervous system, including the dorsal thalamic nucleus, insular cortex, vagus dorsal nucleus, sympathetic ganglia, and enteric nervous system, all of which are implicated in autonomic dysfunction and its associated symptoms [71,72]. Based on these observations, we hypothesize that the longer the duration of the disease in PD patients, the more likely to develop OH, and the presence of OH in PD patients implies that the CNS damage in that patient is extensive. Several limitations must be acknowledged in this study. First, the diagnosis of neurodegenerative diseases relied on clinical assessments, which may lead to issues with diagnostic accuracy. Second, some potential determinants that could influence prevalence, such as the stage of Parkinson's disease, cardiovascular disease, diabetes mellitus, and medications for other conditions, could not be excluded. Third, according to the criteria for orthostatic hypotension (OH), initial OH—occurring very rapidly after rising and thus potentially missed by traditional blood pressure measurements—and delayed OH—occurring after prolonged standing, well beyond the second measurement taken after three minutes of standing—may not have been fully captured, resulting in a possible underestimation. Fourth, the literature we reviewed included two scales: the UPDRS and the MDS-UPDRS. There was some variability in the scoring details of these scales, which may have impacted the accuracy of our meta-analysis results. Finally,our meta-analysis included only studies published in English, which may have introduced a bias by excluding research from other language families. Conclusion The prevalence of OH in PD is 33.1%. Patients with PD and OH tend to be older at examination, have longer disease duration, and exhibit more severe disease manifestations compared to PD patients without OH. Declarations Funding There was no funding for this study. Disclosures All authors have no conflicts of interest to declare. Author contribution HW participated in the study design and wrote the manuscript. HW and CZ independently searched Medline via PubMed, Web of Science, Embase via embase.com, and Cochrane databases for original published studies about the clinical manifestations of PD patients with or without OH. DX reviewed and improved the manuscript. All authors have read and approved the final manuscript. References Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, et al. Consensus statement on the defnition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011.21:69–72 Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M,Tugwell P (2012) NewCastle-Ottawa Quality Assessment Scale [EB/OL]. Rostom A, Dube C, Cranney A. et al. (2004) Celiac disease.Rockville (MD): Agency for Healthcare Research and Quality(US); (Evidence Reports/Technology Assessments, No. 104.) Appendix D. Quality Assessment Forms. DerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp. Clin. Trials. 2007; 28:105–114. Moher D, Liberati A, Tetzlaff J, Altman DG, Group PRISMA. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6:e1000097. Bloem BR, Okun MS, Klein C. Parkinson’s disease. Lancet. 2021;397: 2284-2303. Chaudhuri KR, Healy DG, Schapira AH.Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol.2006;5:235–245. Baschieri F, Calandra-Buonaura G, Doria A, Mastrolilli F, Palareti A, Barletta G, et al. Cardiovascular autonomic testing performed with a new integrated instrumental approach is useful in differentiating MSA-P from PD at an early stage. Parkinsonism Relat Disord 2015;21: 477-482. Velseboer DC, de Haan RJ, Wieling W, Goldstein DS, de Bie RM. Prevalence of orthostatic hypotension in Parkinson’s disease: a systematic review and meta-analysis. Parkinsonism Relat Disord 2011;17:724-729. Klanbut S, Phattanarudee S, Wongwiwatthananukit S, Suthisisang C, Bhidayasiri R. Symptomatic orthostatic hypotension in Parkinson’s disease patients: prevalence, associated factors and its impact on balance confidence. J Neurol Sci 2018;385:168-174. Cersosimo MG, Benarroch EE. Autonomic involvement in Parkinson’s disease: pathology, pathophysiology, clinical features and possible peripheral biomarkers. J Neurol Sci.2012;313:57–63. Schmidt C, Herting B, Prieur S, Junghanns S, Schweitzer K, Globas C,Valsalva manoeuvre in patients with different Parkinsonian disorders.J Neural Transm. 2009;116(7):875-80. Fabrizio Vallelonga, Matteo Valente, Marta Maria Tangari, Anna Covolo, Valeria Milazzo. Hypotensive episodes at 24-h ambulatory blood pressure monitoring predict adverse outcomes in Parkinson's disease.Clin Auton Res. 2024;34(2):281-291. Giovanni Palermo, Alessandro Galgani, Gabriele Bellini, Francesco Lombardo, Nicola Martini.Neurogenic orthostatic hypotension in Parkinson's disease: is there a role for locus coeruleus magnetic resonance imaging?J Neural Transm.2024;131(2):157-164. Yuanyuan Meng, Tianping Tang, Juanjuan Wang, Kun Yu.The correlation of orthostatic hypotension in Parkinson disease with the disease course and severity and its impact on quality of life.Medicine. 2024 ;103(19):e38169. Shanshan Mei, Xue Wang, Wei Mao, Yue Liu, Zichen Tian, Chao Han, Piu Chan.Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson's Disease.NPJ Parkinsons Dis. 2024;11;10(1):173. Kai Bin Lim, Shen-Yang Lim, Jia Wei Hor, Heamah Krishnan, Firdaus Mortadza.Orthostatic hypotension in Parkinson's disease: Sit-to-stand vs. supine-to-stand protocol and clinical correlates.Parkinsonism Relat Disord. 2024:123:106980. Jae Young Joo, Dallah Yoo, Jae-Myoung Kim, Chaewon Shin, Tae-Beom Ahn.Effect of Positional Changes on Cerebral Perfusion in Parkinson’s Disease Patients With Orthostatic Hypotension.J Mov Disord. 2024;17(4):408-415. Gabriele Imbalzano, Claudia Ledda, Marta Maria Tangari, Carlo Alberto Artusi, Elisa Montanaro.Unraveling the stride: exploring the influence of neurogenic orthostatic hypotension on gait and balance in Parkinson's disease.Clin Auton Res. 2024;34(6):593-601. Jillian M Heisler, Jon Toledo-Atucha, Chih-Chun Lin , Harsh N Patel, William G Ondo.Orthostatic hypotension and subjective symptomatic orthostasis in Parkinson's disease: Associations and correlations.Clin Park Relat Disord. 2024;9:11:100262. Timi Earl, Amani Jridi, Perla C Thulin, Meghan Zorn , Kathleen E McKee. Effect of levodopa on postural blood pressure changes in Parkinson disease: a randomized crossover study.Clin Auton Res. 2024;34(1):117-124. Jingrong Zeng, Yingqi Xing, Shanshan Mei, Baolei Xu, Xiaofan Xue, Haixia Song, Erhe Xu.The differences of orthostatic hypotension in patients with Parkinson's disease and multiple system atrophy.Front Neurol. 2023;26:14:1070943. Xiaofan Xue, Anqi Huang, Jingrong Zeng, Haixia Song, Yingqi Xing, Piu Chan, Erhe Xu, Lichun Zhou.The mechanism of impaired delayed recall verbal memory function in Parkinson's disease with orthostatic hypotension: a multiple imaging study.Front Neurol. 2023;18:14:1149577. Iñigo Ruiz Barrio, Yasuo Miki, Zane T. Jaunmuktane, , Thomas Warner, Eduardo De Pablo-Fernandez.Association Between Orthostatic Hypotension and Dementia in Patients With Parkinson Disease and Multiple System Atrophy.Neurology. 2024;12;103(9):e209986. Yi Qin, Zhao-Hui Jin, Zhen-Ying Zhang, Ke-Ke Chen, Xin Yu, Hong-Jiao Yan, Rui-Dan Wang, Yuan Su, Ai-Xian Liu, Jia-Ning Xi, Bo-Yan Fang,et al. Predictive Value of Exercise Blood Pressure Changes for Orthostatic Hypotension in Patients With Parkinson’s Disease.J Clin Neurol. 2023;19(1):67-75. Zhu Liu, Dongning Su, Junhong Zhou, Xuemei Wang , Zhan Wang,et al.Acute effect of levodopa on orthostatic hypotension and its association with motor responsiveness in Parkinson's disease: Results of acute levodopa challenge test. Parkinsonism Relat Disord. 2023:115:105860. Guenson Chevalier, Lucas Udovin, Matilde Otero-Losada, Sofia Bordet, Francisco Capani,ei al.Genetics of Neurogenic Orthostatic Hypotension in Parkinson's Disease, Results from a Cross-Sectional In Silico Study.Brain Sci. 2023:17;13(3):506. Jong Hyeon Ahn, Jin Whan Cho, Jinyoung Youn.Orthostatic Hypotension Is a Predictor of Fatigue in Drug-Naïve Parkinson's Disease.Parkinsons Dis. 2023;8:2023:1700893. Kangfu Yin, Chuanbin Zhou, Yongyun Zhu, Weifang Yin, Lei Yin,et al. REM sleep behavioral disorder may be an independent risk factor for orthostatic hypotension in Parkinson’s disease.Aging Clin Exp Res. 2022;34(1):159-166. Yingqi Xing, Qing Li , Erhe Xu, Jingrong Zeng, Qiuping Li,et al.Impaired Cerebral Autoregulation in Parkinson's Disease: An Orthostatic Hypotension Analysis.Front Neurol. 2022; 18:13:811698. Abenet Tafesse Mengesha.Frequency and Factors Associated with Orthostatic Hypotension in Individuals with Parkinson's Disease: A Case-Control Observational Study.Ethiop J Health Sci. 2022;32(6):1167-1174. Sang-Won Yoo, Joong-Seok Kim, Yoon-Sang Oh, Dong-Woo Ryu, Seunggyun Ha.Cardiac sympathetic burden reflects Parkinson disease burden, regardless of high or low orthostatic blood pressure changes.NPJ Parkinsons Dis. 2021;12;7(1):71. Sang-Won Yoo, Joong-Seok Kim, Ji-Yeon Yoo, Eunkyeong Yun, Uicheul Yoon.Delayed orthostatic hypotension in Parkinson's disease.NPJ Parkinsons Dis. 2021 ;14;7(1):37. Sang-Won Yoo, Seunggyun Ha, Hyukjin Yoon, Ji-Yeon Yoo, Kwang-Soo Lee, et al. Paradoxical Cerebral Perfusion in Parkinson’s Disease Patients with Orthostatic Hypotension: A Dual-Phase 18F-Florbetaben Positron Emission Tomography Study.J Parkinsons Dis. 2021;11(3):1335-1344. Jia-Jing Wu, Hong Jin, Ying-Qi Shao, Cheng-Jie Mao , Jing Chen,et al.Cognition and transcranial sonography in Parkinson’s disease patients with or without orthostatic hypotension.Brain Behav. 2021 ;11(8):e2252. Tadashi Umehara, Hisayoshi Oka, Atsuo Nakahara, Tomotaka Shiraishi, Takeo Sato,et al. Dopaminergic Correlates of Orthostatic Hypotension in de novo Parkinson’s Disease.J Parkinsons Dis. 2021;11(2):665-673. Don Gueu Park, Jae Whan Kim, Young-Sil An, Jaerak Chang, Jung Han Yoon.Plasma neuroflament light chain level and orthostatic hypotension in early Parkinson’s disease.J Neural Transm. 2021;128(12):1853-1861. Lisanne J Dommershuijsen, Alis Heshmatollah, Francesco U S Mattace Raso, Peter J Koudstaal, M Arfan Ikram,et al.Orthostatic Hypotension: A Prodromal Marker of Parkinson's Disease?.Mov Disord. 2021;36(1):164-170. Cecilia Quarracino, Matilde Otero-Losada, Francisco Capani, Santiago Pérez-Lloret.Prevalence and factors related to orthostatic syndromes in recently diagnosed, drug‑naïve patients with Parkinson disease.Clin Auton Res. 2020;30(3):265-271. Tomohiko Nakamura, Masashi Suzuki, Masamichi Ueda, Yumiko Harada, Masaaki Hirayama.Impact of orthostatic hypotension on wheelchair use in patients with Parkinson's disease.J Neural Transm. 2020;127(3):379-383. Sang-Won Yoo, Yoon-Sang Oh, Ji-Yeon Yoo, Dong-Woo Ryu, Kwang-Soo Lee.Intervening Effects of Orthostatic Blood Pressure Change on Subcortical Atrophy and Cognition in De Novo and Drug-Na¨ıve Parkinson’s Disease.J Parkinsons Dis. 2020;10(1):153-160. Katherine Longardner, Ece Bayram, Irene Litvan.Orthostatic Hypotension Is Associated With Cognitive Decline in Parkinson Disease.Front Neurol. 2020;2:11:897. Alessandra Fanciulli, Nicole Campese, Georg Goebel, Jean Pierre Ndayisaba, Sabine Eschlboeck.Association of transient orthostatic hypotension with falls and syncope in patients with Parkinson disease.Neurology. 2020;24;95(21):e2854-e2865. Bonuccelli U, Lucetti C, Del Dotto P, Ceravolo R, Gambaccini G,Bernardini S et al .Orthostatic hypotension in de novo Parkinson disease. Arch Neurol.2003. 60:1400–1404. Matsui H, Nishinaka K, Oda M, Komatsu K, Kubori T, Udaka F.Does cardiac metaiodobenzylguanidine (MIBG) uptake in Parkinson’s disease correlate with major autonomic symptoms? Parkinsonism Relat Disord.2006.12:284–288. Andrew Nataraj, Ali H Rajput.Parkinson's disease, stroke, and related epidemiology.Mov Disord. 2005;20(11):1476-80. Juan Idiaquez, Eduardo E Benarroch, Hugo Rosales, Pablo Milla, Lily Ríos.Autonomic and Cognitive dysfunction in Parkinson’s disease.Clin Auton Res. 2007;17(2):93-8. Sang-Won Yoo, Joong-Seok Kim, Yoon-Sang Oh, Dong-Woo Ryu, Kwang-Soo Lee. Trouble Concentrating is an Easily Overlooked Symptom of Orthostatic Hypotension in Early Parkinson’s Disease.J Parkinsons Dis. 2019;9(2):405-411. Fabrizio Vallelonga, Alberto Romagnolo, Aristide Merola, Gabriele Sobrero, Cristina Di Stefano,et al. Detection of orthostatic hypotension with ambulatory blood pressure monitoring in parkinson’s disease.Hypertens Res. 2019 ;42(10):1552-1560. Fabrizio Vallelonga, Cristina Di Stefano, Aristide Merola, Alberto Romagnolo, Gabriele Sobrero, et al.Blood pressure circadian rhythm alterations in alpha-synucleinopathies.J Neurol. 2019;266(5):1141-1152. Lixia Li, Peng Guo, Duyu Ding, Tenghong Lian, Lijun Zuo, et al. Parkinson’s disease with orthostatic hypotension: analyses of clinical characteristics and influencing factors.Neurol Res. 2019;41(8):734-741. Calogero Edoardo Cicero, Loredana Raciti, Roberto Monastero, Giovanni Mostile, Giulia Donzuso, et al.Cardiovascular autonomic function and MCI in Parkinson's disease.Parkinsonism Relat Disord. 2019:69:55-58. Tadashi Umehara, Hisayoshi Oka, Atsuo Nakahara, Hiromasa Matsuno, Chizuko Toyoda.High norepinephrinergic orthostatic hypotension in early Parkinson's disease.Parkinsonism Relat Disord. 2018:55:97-102. Khushbakht Tanveer, Immad Attique, Waleed Sadiq, Arsalan Ahmad. Non-motor Symptoms in Patients with Parkinson’s Disease: A Cross-sectional Survey. Cureus. 2018;10(10):e3412. Michela Sforza, Francesca Assogna, Domiziana Rinaldi, Giuliano Sette, Stefania Tagliente, et al.Orthostatic hypotension acutely impairs executive functions in Parkinson's disease.Neurol Sci. 2018;39(8):1459-1462. Aristide Merola, Russell P Sawyer, Carlo Alberto Artusi, Ritika Suri, Zoe Berndt.Orthostatic hypotension in Parkinson disease: Impact on health care utilization.Parkinsonism Relat Disord. 2018:47:45-49. Aristide Merola, Alberto Romagnolo, Michela Rosso, Ritika Suri, Zoe Berndt,et al.Autonomic dysfunction in Parkinson's disease: A prospective cohort study.Mov Disord. 2018;33(3):391-397. Daniel O Claassen, Charles H Adler, L Arthur Hewitt, Christopher Gibbons . Characterization of the symptoms of neurogenic orthostatic hypotension and their impact from a survey of patients and caregivers.BMC Neurol. 2018; 25;18(1):125. Schmidt C, Herting B, Prieur S, Junghanns S, Schweitzer K, et al.Valsalva manoeuvre in patients with different Parkinsonian disorders.J Neural Transm. 2009;116(7):875-80. Tomohiko Nakamura, Masaaki Hirayama, Takashi Hara, Yasuaki Mizutani, Junichiro Suzuki, et al.Role of cardiac sympathetic nerves in preventing orthostatic hypotension in Parkinson's disease.Parkinsonism Relat Disord. 2014 ;20(4):409-14. Francesca Baschieri, Giovanna Calandra-Buonaura , Andrea Doria, Francesca Mastrolilli, Aldopaolo Palareti, et al.Cardiovascular autonomic testing performed with a new integrated instrumental approach is useful in differentiating MSA-P from PD at an early stage.Parkinsonism Relat Disord. 2015 ;21(5):477-82. Joong-Seok Kim, Si-Hoon Lee, Yoon-Sang Oh, Jeong-Wook Park, Jae-Young An.Cardiovascular Autonomic Dysfunction in Mild and Advanced Parkinson's Disease.J Mov Disord. 2016 ;9(2):97-103. Seok-Jae Kang, Jin Young Ahn, Joong-Seok Kim, Jin Whan Cho, Ji Young Kim, et al.24-Hour Ambulatory Blood Pressure Monitoring in SWEDDs Patients With Parkinsonism.Can J Neurol Sci. 2016 ;43(3):390-7. Hiroyuki Hatsuta, Masaki Takao, Yuta Nakano, Akane Nogami, Akiko Uchino, et al.Reduction of Small Fibers of Thoracic Ventral Roots and Neurons of Intermediolateral Nucleus in Parkinson Disease and Dementia with Lewy Bodies.J Parkinsons Dis. 2016;6(2):325-34. Jonica Campolo, Renata De Maria, Lorena Cozzi, Marina Parolini, Stefano Bernardi,et al.Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease.J Neurol Sci. 2016:370:167-172. Ahmet Yalcin, Volkan Atmis, Ozlem Karaarslan Cengiz, Esat Cinar, Sevgi Aras, et al.Evaluation of Cardiac Autonomic Functions in Older Parkinson's Disease Patients: a Cross-Sectional Study.Aging Dis. 2016;7(1):28-35. Qirui Jiang Lingyu Zhang, Junyu Lin, Qianqian Wei, Chunyu Li,et al.Orthostatic Hypotension in Multiple System Atrophy: Related Factors and Disease Prognosis.J Parkinsons Dis. 2023;13(8):1313-1320. Feifei Mu, Qian Jiao, Xixun Du, Hong Jiang.Association of orthostatic hypotension with Parkinson's disease: a meta-analysis.Neurol Sci. 2020;41(6):1419-1426. Jiang H, Wang J, Rogers J, Xie J .Brain Iron metabolism dysfunction in Parkinson’s disease. Mol Neurobiol.2017;54:3078–3101. Sulzer D, Edwards RH.The physiological role of alphasynuclein and its relationship to Parkinson’s disease. J Neurochem.2019;150:475–486. Zhang Z, Shi L, Du X, Jiao Q, Jiang H.Acute action of rotenone on excitability of catecholaminergic neurons in rostral ventrolateral medulla. Brain Res Bull.2017;134:151–161. Wang Y, Chen AQ, Xue Y, Liu MF, Liu C, Liu YH, Pan YP, Diao HL, Chen L.Orexins alleviate motor deficits via increasingfiring activity of pallidal neurons in a mouse model of Parkinson’s disease. Am J Physiol Cell Physiol.2019;317:C800–C812. Borghammer, P. & Van Den Berge, N. Brain-First versus Gut-First Parkinson’s disease: a hypothesis. J. Parkinson’s Dis.2019; 9, S281–S295. Borghammer, P. The α-Synuclein Origin and Connectome Model (SOC Model) of Parkinson’s disease: Explaining motor asymmetry, non-motor phenotypes, and cognitive decline. J. Parkinson’s Dis.2021;11, 455–474. Shanshan Mei, Xue Wang, Wei Mao, Yue Liu, Zichen Tian,et al.Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson's Disease.NPJ Parkinsons Dis. 2024;10(1):173. Anthony H V Schapira, K Ray Chaudhuri, Peter Jenner.Non-motor features of Parkinson disease.Nat Rev Neurosci. 2017;18(7):435-450. Vasiliki Katsi, Ilias Papakonstantinou, Eirini Solomou, Alexios S Antonopoulos, Charalambos Vlachopoulos, rt al.Management of Hypertension and Blood Pressure Dysregulation in Patients with Parkinson's Disease-a Systematic Review. Curr Hypertens Rep. 2021;23(5):26. Supplementary Files Cochranesearchmanagersearch.txt SearchingHistory.docx supplementaryfigures.docx Cite Share Download PDF Status: Published Journal Publication published 26 Jul, 2025 Read the published version in Clinical Autonomic Research → Version 1 posted Reviewers agreed at journal 30 Apr, 2025 Reviewers invited by journal 28 Apr, 2025 Editor assigned by journal 27 Apr, 2025 First submitted to journal 27 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6061276","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":449220468,"identity":"f2b6fada-41e2-4b0d-9fb6-c497af7d1657","order_by":0,"name":"Hui Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYBACfv7mgw8+VEjIsbE3EKlFcsaxZMMZZyyM+XgOEKnF4ECOmTRvS0XiPIkEYm1pOJYgObNBgrFN8vHGGww1NtEEtfAzNx8w+LhDgplNOq3YguFYWm4DMbYkzjwjwcYmnWMmwdhwmLAWoF8MDvO2SfCwSZ4hXothM1CLBJsED5FaQIHMOOOMhAEbD9AvCcT4BRiVx398qKirn99+eOONDzU2hLWgOJLoqEHSQqqOUTAKRsEoGBkAAEodQIUBOf51AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-7400-2998","institution":"Sichuan Taikang Hospital Co Ltd","correspondingAuthor":true,"prefix":"","firstName":"Hui","middleName":"","lastName":"Wang","suffix":""},{"id":449220469,"identity":"a88dface-e910-4b5f-ba7f-86e09dc05a2c","order_by":1,"name":"Chi Zhang","email":"","orcid":"","institution":"daping yiyuan: Third Military Medical University Daping Hospital and Research Institute of Surgery","correspondingAuthor":false,"prefix":"","firstName":"Chi","middleName":"","lastName":"Zhang","suffix":""},{"id":449220470,"identity":"44433268-face-4e77-bf8a-2d5f6ea67f08","order_by":2,"name":"Dongxun Xu","email":"","orcid":"","institution":"Sichuan Taikang Hospital Co Ltd","correspondingAuthor":false,"prefix":"","firstName":"Dongxun","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2025-02-19 06:52:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6061276/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6061276/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10286-025-01146-4","type":"published","date":"2025-07-26T15:57:16+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82075219,"identity":"119c2f0c-a7be-4a9a-b541-2adac7a7dbab","added_by":"auto","created_at":"2025-05-06 13:40:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":28450,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of systematic literature searching\u003c/p\u003e","description":"","filename":"Figure1.Flowdiagramblank.png","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/b525007f156e813e25983db9.png"},{"id":82075221,"identity":"e5bc9021-16b6-4f24-afdd-ff4850580ad2","added_by":"auto","created_at":"2025-05-06 13:40:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":785063,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e2.1.\u003c/strong\u003eForest plot on the pooled prevalence of orthostatic hypotension in Parkinson’s disease\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2.\u003c/strong\u003eForest plot of orthostatic hypotension prevalence among Parkinson’s disease patients in European, \u0026nbsp;America(A) and Asian(B) populations.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/45d6dbbed44d8db79cc60e25.png"},{"id":82075773,"identity":"60426613-d00d-472b-ab54-3b61208b90b3","added_by":"auto","created_at":"2025-05-06 13:48:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":250126,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot showing weighted mean difference (WMD) in age between Parkinson’s disease patients with or without orthostatic hypotension.\u003c/p\u003e","description":"","filename":"Figure3.age.png","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/ccb3696a91aae619dd28ff7f.png"},{"id":82075224,"identity":"0e19793f-af14-49f1-a1fe-5f28e87fffa2","added_by":"auto","created_at":"2025-05-06 13:40:43","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":239542,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot showing odds ratio (OR) in sex between Parkinson’s disease patients with or without orthostatic hypotension.\u003c/p\u003e","description":"","filename":"Figure4.sex.png","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/c9e25e115f34a5b24eb7cd08.png"},{"id":82075229,"identity":"e399e2f0-ccf8-45d7-9364-8bc5d4554416","added_by":"auto","created_at":"2025-05-06 13:40:43","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":200254,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot showing weighted mean difference (WMD) in disease duration between Parkinson’s disease patients with or without orthostatic hypotension.\u003c/p\u003e","description":"","filename":"Figure5.diseaseduration.png","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/5edaa424170948b57206fee5.png"},{"id":82076798,"identity":"e0b9c104-658b-48f7-ba6e-b9d4d5df8272","added_by":"auto","created_at":"2025-05-06 13:56:43","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":711165,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot showing Standardized mean difference (SMD) in UPDRS I (A),II (B),III (C) sections and total (D) scores between Parkinson’s disease patients patients with or without orthostatic hypotension.\u003c/p\u003e","description":"","filename":"Figure6UPDRSI.png","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/fd1e2f4b63392f85de3668a4.png"},{"id":82075231,"identity":"904d89d8-12a1-4c5a-9830-c6adaa3320ba","added_by":"auto","created_at":"2025-05-06 13:40:43","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":110930,"visible":true,"origin":"","legend":"\u003cp\u003eBubble plot of meta-regression modeling of III sections scores in Parkinson’s disease with orthostatic hypotension patients adjusted for disease duration.\u003c/p\u003e","description":"","filename":"Figure7.UPDRSIIIregression.png","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/1622396ce1d55e1e5797aee9.png"},{"id":87756681,"identity":"8fb05619-e4a2-4616-b281-ccab8bc0b375","added_by":"auto","created_at":"2025-07-28 16:07:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2384735,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/259cc15a-6659-4153-bc62-da6e5fe06e41.pdf"},{"id":82075776,"identity":"fc672eda-c79a-4adb-a577-399dac17a45a","added_by":"auto","created_at":"2025-05-06 13:48:43","extension":"txt","order_by":21,"title":"","display":"","copyAsset":false,"role":"supplement","size":591,"visible":true,"origin":"","legend":"","description":"","filename":"Cochranesearchmanagersearch.txt","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/e30952e2644b40b5e2fa67cf.txt"},{"id":82075239,"identity":"d6c2334c-4eb3-4819-97e5-251b74253e23","added_by":"auto","created_at":"2025-05-06 13:40:43","extension":"docx","order_by":22,"title":"","display":"","copyAsset":false,"role":"supplement","size":11526,"visible":true,"origin":"","legend":"","description":"","filename":"SearchingHistory.docx","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/2e32c43e18f4bbba4c621ca9.docx"},{"id":82075246,"identity":"3fb4ed67-ca21-4e7e-9c56-87295035b4db","added_by":"auto","created_at":"2025-05-06 13:40:44","extension":"docx","order_by":23,"title":"","display":"","copyAsset":false,"role":"supplement","size":843318,"visible":true,"origin":"","legend":"","description":"","filename":"supplementaryfigures.docx","url":"https://assets-eu.researchsquare.com/files/rs-6061276/v1/fddb34dd0eca09e0c8ca9ed4.docx"}],"financialInterests":"","formattedTitle":"Prevalence and Impact of Orthostatic Hypotension in Parkinson's Disease: A Systematic Review and Meta-Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eParkinson\u0026rsquo;s disease (PD) represents a prevalent neurodegenerative condition, primarily identified by motor manifestations like bradykinesia, rigidity, tremor, and postural instability[6]. Furthermore, non-motor symptoms considerably diminish the quality of life for individuals with PD, which include issues such as constipation, abnormal urination, sexual dysfunction, excessive sweating, and orthostatic hypotension (OH) [7].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOH is recognized as one of the most common forms of cardiovascular autonomic dysfunction in PD, even in its initial stages, with reported prevalence rates between 4.6% and 84.7% [13-66]. It is characterized by a drop of at least 20 mmHg in systolic blood pressure or a minimum of 10 mmHg in diastolic blood pressure within three minutes of assuming an upright position or undergoing a head-up tilt[1]. The condition can result in symptoms like weakness, dizziness, neck pain, falls, and syncope, which underscores its clinical significance [10]. Recent investigations have highlighted the role of several factors, including age, the severity of the disease, medication use, and hypertension, as contributors to the risk of developing OH[10]. Previous studies proposed that PD can be divided into two subtypes: the body-first subtype, where pathological \u0026alpha;-synuclein originates from the peripheral nervous system (PNS), and the brain-first subtype, where \u0026alpha;-synuclein begins in the central nervous system (CNS)[73,74]. Earlier studies indicate that OH might serve as a clinical marker for the \u0026ldquo;body-first\u0026rdquo; subtype of PD, marked by initial autonomic dysfunction, where the heart and peripheral nerves are affected before progression to the central nervous system[75]. Patients with this subtype may experience a more rapid progression towards multisystem involvement[75]. Additionally, PD accompanied by OH is frequently linked to more severe symptoms, such as rapid eye movement sleep behavior disorder (RBD) and cognitive decline[76,77]. Prompt identification of OH is vital, as its occurrence may suggest early indications of multisystem neurologic dysfunction.\u003c/p\u003e\n\u003cp\u003eOH is prevalent in multiple system atrophy (MSA), and MSA patients experiencing OH exhibit more severe disease symptoms than those without OH [67]. The nonmotor symptoms of PD are often overlooked in comparison to the motor symptoms. However, many nonmotor symptoms, such as OH, may impact a patient\u0026apos;s disease progression and quality of life. Therefore, the prevalence of OH in PD and its potential impact on the disease itself equally deserving of our attention. In recent years, there has been a notable increase in studies investigating the effects of OH on disease severity in PD patients compared to earlier research; however, these studies have produced varying results. Some studies indicate that PD patients with OH tend to be older, have a longer disease duration, and exhibit more severe symptoms than their counterparts without OH [16,33]. Conversely, other studies report no significant differences in age, disease duration, or severity between PD patients with and without OH [36,40,45,49]. This reminds us that integrating previous studies for meta-analysis is necessary.\u003c/p\u003e\n\u003cp\u003eThis study presents a comprehensive systematic review and meta-analysis of all published articles concerning the prevalence of OH in PD and its effects on the disease.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eSearching strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO, No. CRD42025636764) and was conducted in accordance with the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)(5). The Cochrane Collaboration definition for systematic review and meta-analysis was strictly followed. Two authors (H. Wang and C. Zhang) independently searched Medline via PubMed, Web of Science, Embase via embase.com, and Cochrane databases for original published studies on the clinical manifestations of PD patients with or without OH. Inclusion criteria were studies published in English between January 2000 and December 2024.The search string was as follows: (\u0026quot;Hypotension, Orthostatic\u0026quot; OR \u0026quot;Hypotension, Postural\u0026quot; OR \u0026quot;Postural Hypotension\u0026quot; OR \u0026quot;Orthostatic Hypotension\u0026quot;) AND (\u0026quot;Idiopathic Parkinson\u0026apos;s Disease\u0026quot; OR \u0026quot;Lewy Body Parkinson\u0026apos;s Disease\u0026quot; OR \u0026quot;Parkinson Disease\u0026quot; OR \u0026quot;Parkinson\u0026apos;s Disease, Idiopathic\u0026quot; OR \u0026quot;Parkinson\u0026apos;s Disease, Lewy Body\u0026quot; OR \u0026quot;Paralysis Agitans\u0026quot; OR \u0026quot;Parkinson\u0026apos;s Disease\u0026quot; OR \u0026quot;Idiopathic Parkinson Disease\u0026quot; OR \u0026quot;Lewy Body Parkinson Disease\u0026quot; OR \u0026quot;Primary Parkinsonism\u0026quot; OR \u0026quot;Parkinsonism, Primary\u0026quot; OR \u0026quot;Parkinson Disease, Idiopathic\u0026quot; OR \u0026quot;Parkinson Disease\u0026quot;).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy selection criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eArticles were initially screened based on their titles and abstracts, with full text consulted when necessary. Patients were diagnosed with OH according to a fall of\u0026nbsp;\u0026ge;20 mmHg systolic or\u0026nbsp;\u0026ge;10 mmHg diastolic blood pressure upon 1\u0026ndash;3 min of active standing or head up tilt [1].\u003c/p\u003e\n\u003cp\u003eInclusion criteria were as follows: (1) studies must be cross-sectional, case-control, or cohort designs published as original research; (2) only studies that investigated the presence of orthostatic hypotension (OH) in more than one underlying disorder were included; (3) the primary outcome of interest was OH; (4) studies needed to provide the prevalence of OH in PD or offer sufficient data to calculate these results; and (5) adequate data must be available to assess differences in the incidence or severity of motor symptoms associated with PD.\u003c/p\u003e\n\u003cp\u003eExclusion criteria were: (1) reviews, editorials, letters, conference abstracts, or case reports; (2) studies focusing exclusively on OH characteristics, pathogenic mechanisms, or PD management related to OH; (3) comparisons between PD and other synucleinopathies; (4) studies with insufficient data for meta-analysis; (5) non-English articles; and (6) studies not involving animal subjects.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDiscrepancies regarding article inclusion were resolved by a third author, D. Xu.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData extraction and study quality assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data extracted from the original articles included the surname of the first author, publication year, country, sample size, method of OH assessment, prevalence of OH, mean age of patients, sex, disease duration, and score on the Unified Parkinson\u0026rsquo;s Disease Rating Scale (UPDRS). For longitudinal studies, only baseline data were extracted.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for case-control and cohort studies, along with the Agency for Healthcare Research and Quality (AHRQ) guidelines for cross-sectional studies [2, 3]. Any discrepancies were resolved through consensus among all authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe STATA software version 16.0 was used for statistical analysis. Odds ratio (OR), weighted mean difference (WMD), or standardized mean difference (SMD) with 95% confidence intervals (95% CI) were used to report pooled results on dichotomous and continuous variables. A pvalue equal to or less than 0.05 was considered statistically significant. Due to the assessment of some included literature using the UPDRS scale while others utilized the MDS-UPDRS scale, which exhibit significant differences in scoring specifications, we conducted our analysis using the Standardized Mean Difference (SMD).The primary outcome measure was frequency of OH in PD as reported in prevalence (%). The pooled prevalence of RBD and 95% confidence intervals were obtained by using a DerSimonian-Laird random-effects model with double arcsine transformation (4). Meta-regression analyses were used to assess whether disease duration affects the UPDRS scores in PD with OH patients. The heterogeneity across studies was evaluated using Cochrane\u0026rsquo;s I\u003csup\u003e2\u003c/sup\u003e values. I\u003csup\u003e2\u003c/sup\u003e \u0026gt; 75% was defined as high heterogeneity, 50% \u0026lt; I\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e\u0026lt; 75% as moderate heterogeneity, 25% \u0026lt; I\u003csup\u003e2\u003c/sup\u003e \u0026lt; 50% as low heterogeneity, and I\u003csup\u003e2\u003c/sup\u003e \u0026lt; 25% as homogeneity. We used a fixed-effects model to meta-analyze data showing homogeneity and low heterogeneity, and a random-effects model to analyze data classified as moderate or high heterogeneity. A sensitivity analysis was performed to detect potential sources of heterogeneity. We used the one by one elimination method on STATA to perform sensitivity analyses to detect potential sources of heterogeneity, and a funnel plot and Begg\u0026rsquo;s test was created to detect publication biases.\u003c/p\u003e"},{"header":"Result","content":"\u003cp\u003eThe literature search identified 3,718 potentially relevant articles (Fig. 1). After the removal of duplicates, 1,326 records were reviewed, resulting in the exclusion of 1,213 during the title and abstract screening phase. Subsequently, 113 full-text articles were assessed for eligibility, of which 59 were excluded for various reasons: 16 were reviews, 6 were studies focused on treatment, 7 were unrelated to PD, 18 were unrelated to OH, 5 were letters, 1 was a case report, and 6 had insufficient data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUltimately, 54 articles were included in our review, encompassing a total of 7,748 PD patients. Among these, 29 original studies were conducted in Asia, 9 in America, 14 in Europe, 1 in Africa, and 1 across multiple continents. A meta-analysis was performed for all PD patients, defined by the prevalence of OH, age, sex, disease duration, and scores on the UPDRS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrevalence of OH\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs demonstrated in Table 1 and Figure 2.1, the summary prevalence of OH in PD, including the results of the present study, was found to be 33.1% (95% CI, 29.3%-37%)\u0026nbsp; from a pooled sample of 7,698 subjects. This study exhibited high heterogeneity (I\u0026sup2; = 93.2%). Furthermore, there was no evidence of publication bias, as indicated by a non-significant result in Begg\u0026apos;s test (Supplementary Figure 1.1.A). Sensitivity analysis confirmed that the results remained unchanged (Supplementary Figure 1.1.B).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs shown in Table 1 and Figure 2.2, the summary prevalence of OH in PD was 31.2% (95% CI, 23.9%-38.5%) in Europe and America, which is comparable to the prevalence in Asia, reported at 34% (95% CI, 30.2%-37.8%). Again, there was no evidence of publication bias, as Begg\u0026apos;s test yielded non-significant results (Supplementary Figures 1.2.A and 1.3.A). Sensitivity analysis also showed consistent results (Supplementary Figures 1.2.B and 1.3.B).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDifferences in age, gender, and disease duration between PD patients with or without OH\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSubgroup analysis based on age included 3,914 patients (Table 2). PD patients with \u0026nbsp;OH were significantly older at the time of examination compared to those without OH (WMD 2.92 years, 95% CI 1.81 to 4.04; I\u0026sup2; = 65.6%; Fig. 3). There was no evidence of publication bias, as Begg\u0026apos;s test yielded a non-significant result (Supplementary Fig. 2.1). The heterogeneity of this study was moderate (I\u0026sup2; = 65.6%). Sensitivity analysis indicated that the results remained unchanged (Supplementary Fig. 2.2).\u003c/p\u003e\n\u003cp\u003eA total of 3,914 patients with PD from 24 studies were included in the analysis by sex (Table 2). No significant difference in sex distribution was observed between PD patients with or without OH (Fig. 4). Our study demonstrated homogeneity (I\u0026sup2; = 0%). Begg\u0026apos;s test did not reveal significant publication bias (Supplementary Fig. 3).\u003c/p\u003e\n\u003cp\u003eA meta-analysis of the disease duration in 3,014 patients with PD from 22 studies indicated that the disease duration in PD patients with OH was significantly longer than in those without OH (WMD 0.71, 95% CI 0.29 to 1.14; Fig. 5). Begg\u0026apos;s test did not show significant publication bias (Supplementary Fig. 4.1). The heterogeneity of this study was moderate (I\u0026sup2; = 71.5%). Sensitivity analysis confirmed that the results remained unchanged (Supplementary Fig. 4.2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDifferences in UPDRS scores between PD patients with or without OH\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 989 patients with PD from 6 studies were included in the analysis of UPDRS part I section scores. The results indicated that there was no significant difference in the distribution of UPDRS part I section scores among Parkinson\u0026apos;s disease patients with or without OH \u0026nbsp;( Fig. 6.A). The heterogeneity of this study was low (I\u0026sup2; =26%). Begg\u0026apos;s test did not reveal significant publication bias (Supplementary Fig. 5.1.1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSimilarly, a total of 989 patients with PD from 6 studies were included in the analysis of UPDRS part II section scores. The results indicated that there was no significant difference in the distribution of UPDRS part II section scores among Parkinson\u0026apos;s disease patients with or without OH ( Fig. 6.B). The heterogeneity of this study was homogeneity (I\u0026sup2; = 16.6%). Begg\u0026apos;s test did not indicate significant publication bias (Supplementary Fig. 5.2.1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA total of 1990 patients with PD from 13 studies were included in the analysis of UPDRS Part III section scores. The results indicated that the UPDRS Part III section scores in PD patients with OH were significantly higher than those in PD patients without OH\u0026nbsp;(SMD 0.41, 95% CI 0.23 to 0.59; Fig. 6.C). Begg\u0026apos;s test did not reveal significant publication bias (Supplementary Fig. 5.3.1). The heterogeneity of this study was moderate (I\u0026sup2; = 64.7%). Sensitivity analysis yielded consistent results (Supplementary Fig. 5.3.2). We conducted meta-regression analyses to evaluate whether disease duration influences the UPDRS part III section scores in PD with OH patients; the findings indicated that disease duration does not\u0026nbsp;affect the statistical results (R\u003csup\u003e2\u003c/sup\u003e=65.03%, P = 0.287; Fig. 7).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAdditionally, a total of 848 patients with PD from 5 studies were included in the analysis of total UPDRS scores. The results indicated that there was no significant difference in the distribution of total UPDRS scores among Parkinson\u0026apos;s disease patients with or without OH (Fig. 6.D). Begg\u0026apos;s test did not indicate significant publication bias (Supplementary Fig. 5.4.1). The heterogeneity of this study was low (I\u0026sup2; = 41.5%).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrevious studies have demonstrated a wide range of prevalence rates for OH in PD, with estimates varying from 4.6% to 84.7% (see Table 1). The meta-analysis conducted in this study revealed a notable prevalence rate of OH among patients with PD, recorded at 33.1%, with a 95% confidence interval ranging from 29.1% to 36.3% (Fig. 2.1). This finding is slightly higher than the results of earlier meta-analyses, which reported a prevalence rate of 27.7% [68]. To mitigate the potential impact of geographic and cultural factors on the observed overall prevalence of OH, we performed separate meta-analyses for the prevalence of OH in patients with PD across Europe, the Americas, and Asia. The results indicated that the summary prevalence of OH in PD was comparable between Europe and the Americas (31.2%) and Asia (34%).\u003c/p\u003e\n\u003cp\u003ePrevious studies have yielded inconsistent findings regarding the variability of age, age of disease duration, and UPDRS scores in patients with PD, both with and without OH. Some studies indicate that PD patients with OH tend to be older, have a longer disease duration, and exhibit more severe symptoms compared to those without OH [16, 33]. However, other studies have not supported these conclusions [36, 40, 45, 49]. To address this disparity, we conducted a meta-analysis encompassing all relevant studies on the impact of OH on PD, thereby increasing the sample size for more robust conclusions. Our analysis revealed that PD patients with OH were significantly older than their counterparts without OH at the time of examination (Fig. 3). Additionally, the disease duration for PD patients with OH was markedly longer than that for those without OH (Fig. 5), and PD patients with OH exhibited significantly higher UPDRS scores across parts 3 section (Fig. 6). These findings indicate that PD patients with OH experience more severe motor symptoms (refer to UPDRS-III section for variability) compared to PD patients without OH.\u003c/p\u003e\n\u003cp\u003eHowever, our findings indicate that PD patients with OH tend to have a longer disease duration, which may result in the manifestation of more severe disease-related symptoms. Consequently, We conducted meta-regression analyses to evaluate whether disease duration influences the UPDRS scores in PD with OH patients. The results revealed that disease duration did not significantly affect the statistical outcomes of the differences in UPDRS-III scores for PD with OH patients. This finding suggests that PD patients with OH may have a longer disease duration, and OH may intensify motor symptoms.\u0026nbsp;The pathological basis of PD primarily involves the degeneration and necrosis of nigrostriatal dopamine neurons, attributed to the formation and aggregation of Lewy bodies [69,70]. In addition to the nigrostriatal system, similar pathological changes can be observed in other regions of the central nervous system, including the dorsal thalamic nucleus, insular cortex, vagus dorsal nucleus, sympathetic ganglia, and enteric nervous system, all of which are implicated in autonomic dysfunction and its associated symptoms [71,72]. Based on these observations, we hypothesize that the longer the duration of the disease in PD patients, the more likely to develop OH, and the presence of OH in PD patients implies that the CNS damage in that patient is extensive.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSeveral limitations must be acknowledged in this study. First, the diagnosis of neurodegenerative diseases relied on clinical assessments, which may lead to issues with diagnostic accuracy. Second, some potential determinants that could influence prevalence, such as the stage of Parkinson\u0026apos;s disease, cardiovascular disease, diabetes mellitus, and medications for other conditions, could not be excluded. Third, according to the criteria for orthostatic hypotension (OH), initial OH\u0026mdash;occurring very rapidly after rising and thus potentially missed by traditional blood pressure measurements\u0026mdash;and delayed OH\u0026mdash;occurring after prolonged standing, well beyond the second measurement taken after three minutes of standing\u0026mdash;may not have been fully captured, resulting in a possible underestimation. Fourth, the literature we reviewed included two scales: the UPDRS and the MDS-UPDRS. There was some variability in the scoring details of these scales, which may have impacted the accuracy of our meta-analysis results. Finally,our meta-analysis included only studies published in English, which may have introduced a bias by excluding research from other language families.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe prevalence of OH in PD is 33.1%. Patients with PD and OH tend to be older at examination, have longer disease duration, and exhibit more severe disease manifestations compared to PD patients without OH.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no funding for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have no conflicts of interest to declare.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHW participated in the study design and wrote the manuscript. HW and CZ independently searched Medline via PubMed, Web of Science, Embase via embase.com, and Cochrane databases for original published studies about the clinical manifestations of PD patients with or without OH. DX reviewed and improved the manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e"},{"header":" References","content":"\u003col\u003e\n \u003cli\u003eFreeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, et al. Consensus statement on the defnition of orthostatic hypotension, neurally mediated syncope and the postural \u0026nbsp;tachycardia syndrome. Clin Auton Res. 2011.21:69\u0026ndash;72\u003c/li\u003e\n \u003cli\u003eWells GA, Shea B, O\u0026rsquo;Connell D, Peterson J, Welch V, Losos M,Tugwell P (2012) NewCastle-Ottawa Quality Assessment Scale [EB/OL].\u003c/li\u003e\n \u003cli\u003eRostom A, Dube C, Cranney A. et al. (2004) Celiac disease.Rockville (MD): Agency for Healthcare Research and Quality(US); (Evidence Reports/Technology Assessments, No. 104.) Appendix D. Quality Assessment Forms.\u003c/li\u003e\n \u003cli\u003eDerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp. Clin. Trials. 2007; 28:105\u0026ndash;114.\u003c/li\u003e\n \u003cli\u003eMoher D, Liberati A, Tetzlaff J, Altman DG, Group PRISMA. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6:e1000097.\u003c/li\u003e\n \u003cli\u003eBloem BR, Okun MS, Klein C. Parkinson\u0026rsquo;s disease. Lancet. 2021;397: 2284-2303.\u003c/li\u003e\n \u003cli\u003eChaudhuri KR, Healy DG, Schapira AH.Non-motor symptoms of Parkinson\u0026rsquo;s disease: diagnosis and management. Lancet Neurol.2006;5:235\u0026ndash;245.\u003c/li\u003e\n \u003cli\u003eBaschieri F, Calandra-Buonaura G, Doria A, Mastrolilli F, Palareti A, Barletta G, et al. Cardiovascular autonomic testing performed with a new integrated instrumental approach is useful in differentiating \u0026nbsp;MSA-P from PD at an early stage. Parkinsonism Relat Disord 2015;21: 477-482.\u003c/li\u003e\n \u003cli\u003eVelseboer DC, de Haan RJ, Wieling W, Goldstein DS, de Bie RM. Prevalence of orthostatic hypotension in Parkinson\u0026rsquo;s disease: a systematic review and meta-analysis. Parkinsonism Relat Disord 2011;17:724-729.\u003c/li\u003e\n \u003cli\u003eKlanbut S, Phattanarudee S, Wongwiwatthananukit S, Suthisisang C, Bhidayasiri R. Symptomatic orthostatic hypotension in Parkinson\u0026rsquo;s \u0026nbsp;disease patients: prevalence, associated factors and its impact on balance confidence. J Neurol Sci 2018;385:168-174.\u003c/li\u003e\n \u003cli\u003eCersosimo MG, Benarroch EE. Autonomic involvement in Parkinson\u0026rsquo;s disease: pathology, pathophysiology, clinical features and possible peripheral biomarkers. J Neurol Sci.2012;313:57\u0026ndash;63.\u003c/li\u003e\n \u003cli\u003eSchmidt C, Herting B, Prieur S, Junghanns S, Schweitzer K, Globas C,Valsalva manoeuvre in patients with different Parkinsonian disorders.J Neural Transm. 2009;116(7):875-80.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eFabrizio Vallelonga, Matteo Valente, Marta Maria Tangari, Anna Covolo, Valeria Milazzo. Hypotensive episodes at 24-h ambulatory blood pressure monitoring predict adverse outcomes in Parkinson\u0026apos;s disease.Clin Auton Res. 2024;34(2):281-291.\u003c/li\u003e\n \u003cli\u003eGiovanni Palermo, Alessandro Galgani, Gabriele Bellini, Francesco Lombardo, Nicola Martini.Neurogenic orthostatic hypotension in Parkinson\u0026apos;s disease: is there a role for locus coeruleus magnetic resonance imaging?J Neural Transm.2024;131(2):157-164.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eYuanyuan Meng, Tianping Tang, Juanjuan Wang, Kun Yu.The correlation of orthostatic hypotension in Parkinson disease with the disease course and severity and its impact on quality of life.Medicine. 2024 ;103(19):e38169.\u003c/li\u003e\n \u003cli\u003eShanshan Mei, Xue Wang, Wei Mao, Yue Liu, Zichen Tian, Chao Han, Piu Chan.Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson\u0026apos;s Disease.NPJ Parkinsons Dis. 2024;11;10(1):173.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKai Bin Lim, Shen-Yang Lim, Jia Wei Hor, Heamah Krishnan, Firdaus Mortadza.Orthostatic hypotension in Parkinson\u0026apos;s disease: Sit-to-stand vs. supine-to-stand protocol and clinical correlates.Parkinsonism Relat Disord. 2024:123:106980.\u003c/li\u003e\n \u003cli\u003eJae Young Joo, Dallah Yoo, Jae-Myoung Kim, Chaewon Shin, Tae-Beom Ahn.Effect of Positional Changes on Cerebral Perfusion in Parkinson\u0026rsquo;s Disease Patients With Orthostatic Hypotension.J Mov Disord. 2024;17(4):408-415.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGabriele Imbalzano, Claudia Ledda, Marta Maria Tangari, Carlo Alberto Artusi, Elisa Montanaro.Unraveling the stride: exploring the influence of neurogenic orthostatic hypotension on gait and balance in Parkinson\u0026apos;s disease.Clin Auton Res. 2024;34(6):593-601.\u003c/li\u003e\n \u003cli\u003eJillian M Heisler, Jon Toledo-Atucha, Chih-Chun Lin , Harsh N Patel, William G Ondo.Orthostatic hypotension and subjective symptomatic orthostasis in Parkinson\u0026apos;s disease: Associations and correlations.Clin Park Relat Disord. 2024;9:11:100262.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTimi Earl, Amani Jridi, Perla C Thulin, Meghan Zorn , Kathleen E McKee. Effect of levodopa on postural blood pressure changes in Parkinson disease: a randomized crossover study.Clin Auton Res. 2024;34(1):117-124.\u003c/li\u003e\n \u003cli\u003eJingrong Zeng, Yingqi Xing, Shanshan Mei, Baolei Xu, Xiaofan Xue, Haixia Song, Erhe Xu.The differences of orthostatic hypotension in patients with Parkinson\u0026apos;s disease and multiple system atrophy.Front Neurol. 2023;26:14:1070943.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eXiaofan Xue, Anqi Huang, Jingrong Zeng, Haixia Song, Yingqi Xing, Piu Chan, Erhe Xu, Lichun Zhou.The mechanism of impaired delayed recall verbal memory function in Parkinson\u0026apos;s disease with orthostatic hypotension: a multiple imaging study.Front Neurol. 2023;18:14:1149577.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eI\u0026ntilde;igo Ruiz Barrio, Yasuo Miki, Zane T. Jaunmuktane, , Thomas Warner, Eduardo De Pablo-Fernandez.Association Between Orthostatic Hypotension and Dementia in Patients With Parkinson Disease and Multiple System Atrophy.Neurology. 2024;12;103(9):e209986.\u003c/li\u003e\n \u003cli\u003eYi Qin, Zhao-Hui Jin, Zhen-Ying Zhang, Ke-Ke Chen, Xin Yu, Hong-Jiao Yan, Rui-Dan Wang, Yuan Su, Ai-Xian Liu, Jia-Ning Xi, Bo-Yan Fang,et al. Predictive Value of Exercise Blood Pressure Changes for Orthostatic Hypotension in Patients With Parkinson\u0026rsquo;s Disease.J Clin Neurol. 2023;19(1):67-75.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eZhu Liu, Dongning Su, Junhong Zhou, Xuemei Wang , Zhan Wang,et al.Acute effect of levodopa on orthostatic hypotension and its association with motor responsiveness in Parkinson\u0026apos;s disease: Results of acute levodopa challenge test. Parkinsonism Relat Disord. 2023:115:105860.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGuenson Chevalier, Lucas Udovin, Matilde Otero-Losada, Sofia Bordet, Francisco Capani,ei al.Genetics of Neurogenic Orthostatic Hypotension in Parkinson\u0026apos;s Disease, Results from a Cross-Sectional In Silico Study.Brain Sci. 2023:17;13(3):506.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eJong Hyeon Ahn, Jin Whan Cho, Jinyoung Youn.Orthostatic Hypotension Is a Predictor of Fatigue in Drug-Na\u0026iuml;ve Parkinson\u0026apos;s Disease.Parkinsons Dis. 2023;8:2023:1700893.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKangfu Yin, Chuanbin Zhou, Yongyun Zhu, Weifang Yin, Lei Yin,et al. REM sleep behavioral disorder may be an independent risk factor for orthostatic hypotension in Parkinson\u0026rsquo;s disease.Aging Clin Exp Res. 2022;34(1):159-166.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eYingqi Xing, Qing Li , Erhe Xu, Jingrong Zeng, Qiuping Li,et al.Impaired Cerebral Autoregulation in Parkinson\u0026apos;s Disease: An Orthostatic Hypotension Analysis.Front Neurol. 2022; 18:13:811698.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAbenet Tafesse Mengesha.Frequency and Factors Associated with Orthostatic Hypotension in Individuals with Parkinson\u0026apos;s Disease: A Case-Control Observational Study.Ethiop J Health Sci. 2022;32(6):1167-1174.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSang-Won Yoo, Joong-Seok Kim, Yoon-Sang Oh, Dong-Woo Ryu, Seunggyun Ha.Cardiac sympathetic burden reflects Parkinson disease burden, regardless of high or low orthostatic blood pressure changes.NPJ Parkinsons Dis. 2021;12;7(1):71.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSang-Won Yoo, Joong-Seok Kim, Ji-Yeon Yoo, Eunkyeong Yun, Uicheul Yoon.Delayed orthostatic hypotension in Parkinson\u0026apos;s disease.NPJ Parkinsons Dis. 2021 ;14;7(1):37.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSang-Won Yoo, Seunggyun Ha, Hyukjin Yoon, Ji-Yeon Yoo, Kwang-Soo Lee, et al. Paradoxical Cerebral Perfusion in Parkinson\u0026rsquo;s Disease Patients with Orthostatic Hypotension: A Dual-Phase 18F-Florbetaben Positron Emission Tomography Study.J Parkinsons Dis. 2021;11(3):1335-1344.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eJia-Jing Wu, Hong Jin, Ying-Qi Shao, Cheng-Jie Mao , Jing Chen,et al.Cognition and transcranial sonography in Parkinson\u0026rsquo;s disease patients with or without orthostatic hypotension.Brain Behav. 2021 ;11(8):e2252.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTadashi Umehara, Hisayoshi Oka, Atsuo Nakahara, Tomotaka Shiraishi, Takeo Sato,et al. Dopaminergic Correlates of Orthostatic Hypotension in de novo Parkinson\u0026rsquo;s Disease.J Parkinsons Dis. 2021;11(2):665-673.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDon Gueu Park, Jae Whan Kim, Young-Sil An, Jaerak Chang, Jung Han Yoon.Plasma neuroflament light chain level and orthostatic hypotension in early Parkinson\u0026rsquo;s disease.J Neural Transm. 2021;128(12):1853-1861.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLisanne J Dommershuijsen, Alis Heshmatollah, Francesco U S Mattace Raso, Peter J Koudstaal, M Arfan Ikram,et al.Orthostatic Hypotension: A Prodromal Marker of Parkinson\u0026apos;s Disease?.Mov Disord. 2021;36(1):164-170.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCecilia Quarracino, Matilde Otero-Losada, Francisco Capani, Santiago P\u0026eacute;rez-Lloret.Prevalence and factors related to orthostatic syndromes in recently \u0026nbsp; diagnosed, drug‑na\u0026iuml;ve patients with Parkinson disease.Clin Auton Res. 2020;30(3):265-271.\u003c/li\u003e\n \u003cli\u003eTomohiko Nakamura, Masashi Suzuki, Masamichi Ueda, Yumiko Harada, Masaaki Hirayama.Impact of orthostatic hypotension on wheelchair use in patients with Parkinson\u0026apos;s disease.J Neural Transm. 2020;127(3):379-383.\u003c/li\u003e\n \u003cli\u003eSang-Won Yoo, Yoon-Sang Oh, Ji-Yeon Yoo, Dong-Woo Ryu, Kwang-Soo Lee.Intervening Effects of Orthostatic Blood Pressure Change on Subcortical Atrophy and Cognition in De Novo and Drug-Na\u0026uml;ıve Parkinson\u0026rsquo;s Disease.J Parkinsons Dis. 2020;10(1):153-160.\u003c/li\u003e\n \u003cli\u003eKatherine Longardner, Ece Bayram, Irene Litvan.Orthostatic Hypotension Is Associated With Cognitive Decline in Parkinson Disease.Front Neurol. 2020;2:11:897.\u003c/li\u003e\n \u003cli\u003eAlessandra Fanciulli, Nicole Campese, Georg Goebel, Jean Pierre Ndayisaba, Sabine Eschlboeck.Association of transient orthostatic hypotension with falls and syncope in patients with Parkinson disease.Neurology. 2020;24;95(21):e2854-e2865.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBonuccelli U, Lucetti C, Del Dotto P, Ceravolo R, Gambaccini G,Bernardini S et al .Orthostatic hypotension in de novo Parkinson disease. Arch Neurol.2003. 60:1400\u0026ndash;1404.\u003c/li\u003e\n \u003cli\u003eMatsui H, Nishinaka K, Oda M, Komatsu K, Kubori T, Udaka F.Does cardiac metaiodobenzylguanidine (MIBG) uptake in Parkinson\u0026rsquo;s disease correlate with major autonomic symptoms? Parkinsonism Relat Disord.2006.12:284\u0026ndash;288.\u003c/li\u003e\n \u003cli\u003eAndrew Nataraj, Ali H Rajput.Parkinson\u0026apos;s disease, stroke, and related epidemiology.Mov Disord. 2005;20(11):1476-80.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eJuan Idiaquez, Eduardo E Benarroch, Hugo Rosales, Pablo Milla, Lily R\u0026iacute;os.Autonomic and Cognitive dysfunction in Parkinson\u0026rsquo;s disease.Clin Auton Res. 2007;17(2):93-8.\u003c/li\u003e\n \u003cli\u003eSang-Won Yoo, Joong-Seok Kim, Yoon-Sang Oh, Dong-Woo Ryu, Kwang-Soo Lee. Trouble Concentrating is an Easily Overlooked Symptom of Orthostatic Hypotension in Early Parkinson\u0026rsquo;s Disease.J Parkinsons Dis. 2019;9(2):405-411.\u003c/li\u003e\n \u003cli\u003eFabrizio Vallelonga, Alberto Romagnolo, Aristide Merola, Gabriele Sobrero, Cristina Di Stefano,et al. Detection of orthostatic hypotension with ambulatory blood pressure monitoring in parkinson\u0026rsquo;s disease.Hypertens Res. 2019 ;42(10):1552-1560.\u003c/li\u003e\n \u003cli\u003eFabrizio Vallelonga, Cristina Di Stefano, Aristide Merola, Alberto Romagnolo, Gabriele Sobrero, et al.Blood pressure circadian rhythm alterations in alpha-synucleinopathies.J Neurol. 2019;266(5):1141-1152.\u003c/li\u003e\n \u003cli\u003eLixia Li, Peng Guo, Duyu Ding, Tenghong Lian, Lijun Zuo, et al. Parkinson\u0026rsquo;s disease with orthostatic hypotension: analyses of clinical characteristics and influencing factors.Neurol Res. 2019;41(8):734-741.\u003c/li\u003e\n \u003cli\u003eCalogero Edoardo Cicero, Loredana Raciti, Roberto Monastero, Giovanni Mostile, Giulia Donzuso, et al.Cardiovascular autonomic function and MCI in Parkinson\u0026apos;s disease.Parkinsonism Relat Disord. 2019:69:55-58.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTadashi Umehara, Hisayoshi Oka, Atsuo Nakahara, Hiromasa Matsuno, Chizuko Toyoda.High norepinephrinergic orthostatic hypotension in early Parkinson\u0026apos;s disease.Parkinsonism Relat Disord. 2018:55:97-102.\u003c/li\u003e\n \u003cli\u003eKhushbakht Tanveer, Immad Attique, Waleed Sadiq, Arsalan Ahmad. Non-motor Symptoms in Patients with Parkinson\u0026rsquo;s Disease: A Cross-sectional Survey. Cureus. 2018;10(10):e3412.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMichela Sforza, Francesca Assogna, Domiziana Rinaldi, Giuliano Sette, Stefania Tagliente, et al.Orthostatic hypotension acutely impairs executive functions in Parkinson\u0026apos;s disease.Neurol Sci. 2018;39(8):1459-1462.\u003c/li\u003e\n \u003cli\u003eAristide Merola, Russell P Sawyer, Carlo Alberto Artusi, Ritika Suri, Zoe Berndt.Orthostatic hypotension in Parkinson disease: Impact on health care utilization.Parkinsonism Relat Disord. 2018:47:45-49.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAristide Merola, Alberto Romagnolo, Michela Rosso, Ritika Suri, Zoe Berndt,et al.Autonomic dysfunction in Parkinson\u0026apos;s disease: A prospective cohort study.Mov Disord. 2018;33(3):391-397.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDaniel O Claassen, Charles H Adler, L Arthur Hewitt, Christopher Gibbons . Characterization of the symptoms of neurogenic orthostatic hypotension and their impact from a survey of patients and caregivers.BMC Neurol. 2018; 25;18(1):125.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSchmidt C, Herting B, Prieur S, Junghanns S, Schweitzer K, et al.Valsalva manoeuvre in patients with different Parkinsonian disorders.J Neural Transm. 2009;116(7):875-80.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTomohiko Nakamura, Masaaki Hirayama, Takashi Hara, Yasuaki Mizutani, Junichiro Suzuki, et al.Role of cardiac sympathetic nerves in preventing orthostatic hypotension in Parkinson\u0026apos;s disease.Parkinsonism Relat Disord. 2014 ;20(4):409-14.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eFrancesca Baschieri, Giovanna Calandra-Buonaura , Andrea Doria, Francesca Mastrolilli, Aldopaolo Palareti, et al.Cardiovascular autonomic testing performed with a new integrated instrumental approach is useful in differentiating MSA-P from PD at an early stage.Parkinsonism Relat Disord. 2015 ;21(5):477-82.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eJoong-Seok Kim, Si-Hoon Lee, Yoon-Sang Oh, Jeong-Wook Park, Jae-Young An.Cardiovascular Autonomic Dysfunction in Mild and Advanced Parkinson\u0026apos;s Disease.J Mov Disord. 2016 ;9(2):97-103.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSeok-Jae Kang, Jin Young Ahn, Joong-Seok Kim, Jin Whan Cho, Ji Young Kim, et al.24-Hour Ambulatory Blood Pressure Monitoring in SWEDDs Patients With Parkinsonism.Can J Neurol Sci. 2016 ;43(3):390-7.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHiroyuki Hatsuta, Masaki Takao, Yuta Nakano, Akane Nogami, Akiko Uchino, et al.Reduction of Small Fibers of Thoracic Ventral Roots and Neurons of Intermediolateral Nucleus in Parkinson Disease and Dementia with Lewy Bodies.J Parkinsons Dis. 2016;6(2):325-34.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eJonica Campolo, Renata De Maria, Lorena Cozzi, Marina Parolini, Stefano Bernardi,et al.Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson\u0026apos;s disease.J Neurol Sci. 2016:370:167-172.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAhmet Yalcin, Volkan Atmis, Ozlem Karaarslan Cengiz, Esat Cinar, Sevgi Aras, et al.Evaluation of Cardiac Autonomic Functions in Older Parkinson\u0026apos;s Disease Patients: a Cross-Sectional Study.Aging Dis. 2016;7(1):28-35.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eQirui Jiang Lingyu Zhang, Junyu Lin, Qianqian Wei, Chunyu Li,et al.Orthostatic Hypotension in Multiple System Atrophy: Related Factors and Disease Prognosis.J Parkinsons Dis. 2023;13(8):1313-1320.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eFeifei Mu, Qian Jiao, Xixun Du, Hong Jiang.Association of orthostatic hypotension with Parkinson\u0026apos;s disease: a meta-analysis.Neurol Sci. 2020;41(6):1419-1426.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eJiang H, Wang J, Rogers J, Xie J .Brain Iron metabolism dysfunction in Parkinson\u0026rsquo;s disease. Mol Neurobiol.2017;54:3078\u0026ndash;3101.\u003c/li\u003e\n \u003cli\u003eSulzer D, Edwards RH.The physiological role of alphasynuclein and its relationship to Parkinson\u0026rsquo;s disease. J Neurochem.2019;150:475\u0026ndash;486.\u003c/li\u003e\n \u003cli\u003eZhang Z, Shi L, Du X, Jiao Q, Jiang H.Acute action of rotenone on excitability of catecholaminergic neurons in rostral ventrolateral medulla. Brain Res Bull.2017;134:151\u0026ndash;161.\u003c/li\u003e\n \u003cli\u003eWang Y, Chen AQ, Xue Y, Liu MF, Liu C, Liu YH, Pan YP, Diao HL, Chen L.Orexins alleviate motor deficits via increasingfiring activity of pallidal neurons in a mouse model of Parkinson\u0026rsquo;s disease. Am J Physiol Cell Physiol.2019;317:C800\u0026ndash;C812.\u003c/li\u003e\n \u003cli\u003eBorghammer, P. \u0026amp; Van Den Berge, N. Brain-First versus Gut-First Parkinson\u0026rsquo;s disease: a hypothesis. J. Parkinson\u0026rsquo;s Dis.2019; 9, S281\u0026ndash;S295.\u003c/li\u003e\n \u003cli\u003eBorghammer, P. The \u0026alpha;-Synuclein Origin and Connectome Model (SOC Model) of Parkinson\u0026rsquo;s disease: Explaining motor asymmetry, non-motor phenotypes, and cognitive decline. J. Parkinson\u0026rsquo;s Dis.2021;11, 455\u0026ndash;474.\u003c/li\u003e\n \u003cli\u003eShanshan Mei, Xue Wang, Wei Mao, Yue Liu, Zichen Tian,et al.Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson\u0026apos;s Disease.NPJ Parkinsons Dis. 2024;10(1):173.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAnthony H V Schapira, K Ray Chaudhuri, Peter Jenner.Non-motor features of Parkinson disease.Nat Rev Neurosci. 2017;18(7):435-450.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eVasiliki Katsi, Ilias Papakonstantinou, Eirini Solomou, Alexios S Antonopoulos, Charalambos Vlachopoulos, rt al.Management of Hypertension and Blood Pressure Dysregulation in Patients with Parkinson\u0026apos;s Disease-a Systematic Review. Curr Hypertens Rep. 2021;23(5):26.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"clinical-autonomic-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"autr","sideBox":"Learn more about [Clinical Autonomic Research](http://link.springer.com/journal/10286)","snPcode":"10286","submissionUrl":"https://www.editorialmanager.com/autr/default2.aspx","title":"Clinical Autonomic Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6061276/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6061276/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e Parkinson’s disease (PD) is frequently associated with orthostatic hypotension (OH). Research on the prevalence of OH in PD and its effects on patients has produced inconsistent findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA systematic review and meta-analysis were performed by searching for studies related to PD and OH in the PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled as necessary to calculate the prevalence of OH in PD patients, along with odds ratios (OR), weighted mean differences (WMD), or standardized mean difference (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I²statistic.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The prevalence of OH in patients with PD was found to be 33.1% (95% CI, 29.3%-37%) in a pooled sample of 7,748 subjects. Patients with PD and OH were significantly older at the time of examination (WMD 2.92 years) and had a longer disease duration (WMD 0.71 years) compared to those without OH. There was no significant difference in the distribution of sex, or in the scores of Unified Parkinson's Disease Rating Scale (UPDRS) parts I and II, as well as the total scores among Parkinson's disease patients with or without OH. Additionally, PD patients with OH exhibited significantly higher UPDRS scores across part 3 section scores (SMD 0.41, 95% CI 0.23 to 0.59).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The prevalence of OH in PD is 33.1%. Patients with PD and OH are generally older at examination, have a longer disease duration, and display more severe disease manifestations compared to those without OH.\u003c/p\u003e","manuscriptTitle":"Prevalence and Impact of Orthostatic Hypotension in Parkinson's Disease: A Systematic Review and Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-06 13:40:38","doi":"10.21203/rs.3.rs-6061276/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-04-30T12:47:52+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-28T15:46:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-28T03:00:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Clinical Autonomic Research","date":"2025-04-27T21:11:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"clinical-autonomic-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"autr","sideBox":"Learn more about [Clinical Autonomic Research](http://link.springer.com/journal/10286)","snPcode":"10286","submissionUrl":"https://www.editorialmanager.com/autr/default2.aspx","title":"Clinical Autonomic Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5807076f-9076-4024-bd71-fa477569492f","owner":[],"postedDate":"May 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-28T16:00:20+00:00","versionOfRecord":{"articleIdentity":"rs-6061276","link":"https://doi.org/10.1007/s10286-025-01146-4","journal":{"identity":"clinical-autonomic-research","isVorOnly":false,"title":"Clinical Autonomic Research"},"publishedOn":"2025-07-26 15:57:16","publishedOnDateReadable":"July 26th, 2025"},"versionCreatedAt":"2025-05-06 13:40:38","video":"","vorDoi":"10.1007/s10286-025-01146-4","vorDoiUrl":"https://doi.org/10.1007/s10286-025-01146-4","workflowStages":[]},"version":"v1","identity":"rs-6061276","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6061276","identity":"rs-6061276","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}