Orthostatic Hypotension In Parkinson's Disease Research Articles

The correlation of orthostatic hypotension in Parkinson disease with the disease course and severity and its impact on quality of life.

We investigated the correlation of orthostatic hypotension (OH) in Parkinson disease (PD) with the disease course and severity, and its possible impact on quality of life. 171 PD patients were recruited and divided into the PD-NOH (n = 91) and PD-OH groups (n = 80). Clinical data were collected. The severity and quality of life of PD patients were evaluated. The impact of disease severity was analyzed using logistic regression analysis. The ROC curve was plotted. There were significant differences (P < .05) between PD-NOH and PD-OH groups in terms of the disease course, non-motor symptoms (somnipathy), Hoehn&Yahr stage, LEDD score, RBDSQ score, PDQ-39 score, MMSE score, MoCA, MDS-UPDRS Part III scores during off- and on-periods, and NMSS score. Hoehn&Yahr stage (OR 4.950, 95% CI 1.516-16.157, P = .008) was closely associated with the risk of OH in PD. PDQ-39 score (OR 1.079, 95% CI 1.033-1.127, P = .001) in PD patients with OH further decreased. Patients with PD-OH experienced severe impairment in 4 dimensions of quality of life, including motor function, cognitive function, physical discomfort, and activities of daily living. Different clinical symptoms of PD-OH were positively correlated with PDQ39 subscales. The area under the ROC curve of the Hoehn&Yahr stage in predicting the occurrence of OH was 0.679 (95% CI 0.600-0.758), and that of the Hoehn&Yahr stage combined with levodopa equivalent dose, and MDS-UPDRS Part III score during off-period was 0.793 (95% CI 0.727-0.862). Higher Hoehn&Yahr stage is associated with increased risk of OH in PD patients, and deteriorated quality of life of PD patients. Patients with different OH symptoms are affected in different dimensions of their quality of life. The Hoehn & Yahr stage can independently predict the risk of OH in PD patients.

Orthostatic hypotension in Parkinson's disease: Sit-to-stand vs. supine-to-stand protocol and clinical correlates

BackgroundScreening for orthostatic hypotension (OH) is integral in Parkinson's disease (PD) management, yet evidence-based guidelines on best practice methods for diagnosing OH in PD are lacking. MethodsWe investigated the frequency and correlates of OH, symptomatic OH, and neurogenic OH, in a large consecutively recruited PD cohort (n = 318), and compared the diagnostic performance of the sit-to-stand vs. the supine-to-stand blood pressure (BP) test. We evaluated the utility of continuous BP monitoring and tilt table testing in patients with postural symptoms or falls who were undetected to have OH with clinic-based BP measurements. Disease severity, fluid intake, orthostatic and overactive bladder symptoms, falls, comorbidities and medication history were evaluated. ResultsPatients’ mean age was 66.1 ± 9.5years, with mean disease duration 7.8 ± 5.5years. OH frequency was 35.8 % based on the supine-to-stand test. OH in PD was significantly associated with older age, lower body mass index, longer disease duration, worse motor, cognitive and overactive bladder symptoms and functional disabilities, falls, and lower fluid intake. A similar profile was seen with asymptomatic OH. Three quarters of OH were neurogenic, with the majority also having supine hypertension. The sit-to-stand test had a sensitivity of only 0.39. One quarter of patients were additionally diagnosed with OH during continuous BP monitoring. ConclusionsThe sit-to-stand test substantially underdiagnoses OH in PD, with the important practice implication that supine-to-stand measurements may be preferred. Screening for OH is warranted even in asymptomatic patients. Adequate fluid intake, treatment of urinary dysfunction and falls prevention are important strategies in managing PD patients with OH.

Orthostatic Hypotension in Parkinson Disease: What Is New?

Orthostatic hypotension (OH) is the primary manifestation of cardiovascular autonomic dysfunction in Parkinson disease (PD) and can be a prodromal feature of the disease. We review the recent progress in the field of autonomic dysfunction in PD. Individuals with isolated neurogenic OH should be followed up frequently because they may evolve into PD, dementia with Lewy bodies, or multiple system atrophy. The prevalence of OH in PD increases with disease stages, but the role of levodopa remains unclear. Measurement of supine and standing heart rate and blood pressure allows for accurate identification of neurogenic OH in the clinic. Accurate identification of neurogenic OH in the clinic is crucial for identification of individuals who may benefit from participation in neuroprotective trials in the future. The treatment of OH in PD should be individualized and may reduce the risk of falls, cognitive impairment, and death.

Annals for Educators - 5 May 2020.

Annals for Educators - 5 May 2020.

Association of orthostatic hypotension with Parkinson's disease: a meta-analysis.

Orthostatic hypotension (OH) is a common non-motor sign of Parkinson's disease (PD). Several epidemiological studies have estimated the association between OH and PD with controversial results. Here, a meta-analysis was conducted to evaluate the association between them. PubMed, Embase, Web of Science, CNKI (Chinese National Knowledge Infrastructure), VIP (Database of Chinese Scientific and Technical Periodicals), and Wanfang databases were searched for eligible publications from October 2003 to December 2017. Prevalence numbers from studies were pooled using a non-linear random-effects meta-analysis. Random effect model was used to calculatethe pooled odds ratio (OR) with 95% confidence intervals (CIs) from individual studies. Publication bias was estimated by Egger's test, Begg's test, and the funnel plot. Nineteen studies involving 1620 PD patients and 898 healthy controls were included in this meta-analysis. The pooled estimate of the prevalence of OH in PD was 27.7% compared with 7.9% of that in control. The pooled OR of OH with PD was 4.343 (95% CI3.323-5.676) with a low heterogeneity (I2= 12.5%, Pheterogeneity = 0.301). In the present meta-analysis, the pooled OR of OH with PD was 4.343 (95% CI 3.323-5.676) with a low heterogeneity, which showed a significant association between OH and increased risk of PD.

Orthostatic hypotension in Parkinson disease: A 7-year prospective population-based study.

To determine the frequency, evolution, and associated features of orthostatic hypotension (OH) over 7 years of prospective follow-up in a population-based, initially drug-naive Parkinson disease (PD) cohort. We performed repeated lying and standing blood pressure measurements in 185 patients with newly diagnosed PD and 172 matched normal controls to determine the occurrence of (1) OH using consensus-based criteria and (2) clinically significant OH (mean arterial pressure in standing position ≤75 mm Hg). We applied generalized estimating equations models for correlated data to investigate associated features of these 2 outcomes in patients with PD. OH was more common in patients with PD than controls at all visits, with the relative risk increasing from 3.0 (95% confidence interval [CI] 1.6-5.8; p < 0.001) at baseline to 4.9 (95% CI 2.4-10.1; p < 0.001) after 7 years. Despite a high cumulative prevalence of OH (65.4%) and clinically significant OH (29.2%), use of antihypotensive drugs was very rare (0.5%). OH was independently associated with older age (odds ratio [OR] 1.06 per year; 95% CI 1.03-1.10), lower Mini-Mental State Examination score (OR 0.91 [0.85-0.97] per unit), and longer follow-up time (OR 1.12 [1.03-1.23] per year). Clinically significant OH was associated with the same characteristics, in addition to higher levodopa equivalent dosage (OR 1.16 [1.07-1.25] per 100 mg). In this population-based study, we found OH to be a very frequent but undertreated complication in early PD, with associations to both disease-specific symptoms and drug treatment. Our findings suggest that clinicians should more actively assess and manage OH abnormalities in PD.

High norepinephrinergic orthostatic hypotension in early Parkinson's disease

IntroductionPlasma norepinephrine concentration reflects lesions causing OH. We investigate whether patients with high norepinephrinergic orthostatic hypotension (OH) whose supine plasma norepinephrine concentration (NEsupine) is above the mean value in all patients with Parkinson's disease (PD) have central sympathetic denervation. MethodsWe analyzed data from 110 non-demented patients with early de novo PD who underwent cardiovascular examinations. We divided the patients into three groups according to the presence or absence of orthostatic hypotension and NEsupine: patients without OH, patients with OH+high NEsupine, and patients with OH+low NEsupine. ResultsThe mean NEsupine in all patients was 251.6 pg/ml. Twelve patients (10.9%) had OH+high NEsupine (≥251.6 pg/ml), and 45 patients (40.9%) had OH+low NEsupine (<251.6 pg/ml). OH was more pronounced in patients with OH+high NEsupine than in those with OH+low NEsupine (p = 0.024). Vasopressin release and percent increase of NE after orthostatic stress were well preserved in patients with OH+low NEsupine, but not in patients with OH+high NEsupine. Cognition was lower in patients with OH+high NEsupine than in patients with OH+low NEsupine (p = 0.019) and was associated with vasopressin release during orthostatic stress on multiple regression analysis. The degree of cardiac sympathetic denervation did not differ between two groups with OH. ConclusionsPatient with PD and high norepinephrinergic OH are a subset of patients who have early cognitive decline and impaired vasopressin release. Vasopressin release after orthostatic stress was closely related to global cognition in PD.

Orthostatic hypotension in Parkinson disease: Impact on health care utilization

IntroductionOrthostatic hypotension (OH) represents a frequent yet overlooked source of disability in Parkinson disease (PD). In particular, its impact on health care utilization has been insufficiently examined. We sought to determine the differential health care utilization in PD patients with (PDOH+) and without OH (PDOH−). MethodsWe quantified the emergency room (ER) visits, hospitalizations, outpatient clinic evaluations, phone calls, and e-mails from PD patients on whom supine and orthostatic blood pressure (BP) measurements were obtained during routine clinical practice between June 2013 and July 2016. Comparative costs between PDOH+ and PDOH− were adjusted for age, disease duration, motor severity, levodopa equivalent daily dose, and Montreal Cognitive Assessment. ResultsFrom a total of 317 PD patients, 29.3% were classified as PDOH+ (n = 93) and 70.6% as PDOH− (n = 224) over 30.2 ± 11.0 months, in which there were 247 hospitalizations, 170 ER visits, 2386 outpatient evaluations, and 4747 telephone calls/e-mails. After-adjusting for relevant covariates, PDOH+ was associated with more hospitalization days (+285%; p = 0.041), ER visits (+152%; p = 0.045), and telephone calls/e-mails than PDOH− (+142%; p = 0.009). The overall health care-related cost in PDOH+ was 2.5-fold higher than for PDOH− ($25,205 ± $6546 vs. $9831 ± $4167/person/year; p = 0.037). ConclusionOH increases health care utilization in PD independently from age, disease duration, motor severity, dopaminergic treatment, and cognitive function.

Domperidone for Hypotension in Parkinson's Disease: A Systematic Review.

Domperidone is a proposed treatment of orthostatic hypotension (OH) in Parkinson's disease (PD). However, domperidone use in PD is tempered by concerns regarding QT prolongation and ventricular tachyarrhythmia and sudden cardiac death (VT/SCD). The aim is to identify peer-reviewed studies in which either (1) the effect of domperidone on blood pressure in patients with PD, or (2) the adverse effects associated with domperidone use in PD patients has been reported. PubMed, EMBASE, Medline and Scopus were searched using the terms Parkinson's disease and domperidone. Twenty-two articles fulfilled the inclusion criteria. One study was a randomized placebo-controlled trial with domperidone administration independent of the commencement of dopaminergic medications. This study identified a non-statistically significant trend that domperidone may be beneficial for OH in PD. Several studies identified statistically significant differences in BP with domperidone in the setting of initiating dopaminergic medication. There is currently the most evidence to support domperidone use with apomorphine commencement. Studies reporting domperidone adverse effects in PD patients were largely retrospective or cross-sectional. The identified studies demonstrated that domperidone may cause QT prolongation and is associated with increased risk of VT/SCD in PD patients with preexisting cardiac disease. Domperidone may help to ameliorate OH associated with dopaminergic medications in PD, namely when used in conjunction with apomorphine. When considering whether to use domperidone in PD, factors that should be taken into account include pre-existing heart disease and drug interactions, as well as the impact of OH on mobility, cognition and quality of life.

Evaluation of orthostatic hypotension in Parkinson disease by measuring the catecholamine level and using a Cardiac MIBG scintigraphy

Background: Orthostatic hypotension (OH) is one of the non-motor manifestations of Parkinson disease (PD), however the responsible lesion of OH in PD is still unclear.

Cardiac sympathetic denervation and dementia in de novo Parkinson's disease: A 7-year follow-up study

BackgroundPostganglionic cardiac sympathetic denervation is evident in patients with early-stage Parkinson's disease (PD). Cardiac iodine-123-meta-iodobenzylguanidine (MIBG) uptake is correlated with the non-motor symptoms of PD, suggesting that low cardiac MIBG uptake may reflect wider alpha-synuclein pathology. In addition, low cardiac MIBG could be related to orthostatic hypotension in PD, which may affect cognition. However, the prognostic validity of baseline MIBG scintigraphy in terms of the risk of subsequent dementia remains unclear. We investigated whether cardiac MIBG uptake was associated with a later risk of dementia. MethodsWe retrospectively enrolled 93 drug-naive patients with de novo PD who underwent MIBG scanning on initial evaluation. The patients visited our outpatient clinic every 3–6months and were followed-up for a minimum of 4years from the time they were begun on dopaminergic medication. The predictive powers of baseline MIBG cardiac scintigraphic data in terms of dementia development were evaluated using Cox's proportional hazard models. ResultsDuring a mean follow-up period of 6.7years, 27 patients with PD (29.0%) developed dementia. These patients had less baseline MIBG uptake than did others (delayed H/M ratios: 1.19 vs. 1.31). Multivariate Cox's proportional hazard modeling revealed that both MIBG uptake (hazard ratio [HR] 3.40; p=0.004) and age (HR 1.08, p=0.01) significantly predicted dementia development. ConclusionA reduction in cardiac MIBG uptake by PD patients may be associated with a subsequent risk of dementia; reduced uptake may reflect wider extension of alpha-synuclein pathology in PD.

Orthostatic hypotension predicts motor decline in early Parkinson disease

BackgroundOrthostatic hypotension is increasingly reported as a risk factor for development of late-stage disease features in Parkinson disease (PD). Less is known about its significance in individuals with early PD who are often targeted for neuroprotective trials. MethodsUsing data from the CALM-PD trial (n = 275), we explored whether early orthostatic hypotension predicts a decline in the Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living) or UDPRS III (motor) score after 102 weeks. We also explored risk factors for worsening orthostatic hypotension over a nearly 2-year period. ResultsAfter controlling for age, disease duration, gender, study drug, change in mini-mental status exam score, levodopa equivalent dose, and baseline UPDRS II or III score respectively, the degree of orthostatic hypotension at enrollment associated with a worsening in UPDRS motor score (t = 2.40, p = 0.017) at week 102 but not with UPDRS ADL score (t = 0.83, p = 0.409). Worsening in orthostatic hypotension during the study associated with longer disease duration (t = 2.37, p = 0.019) and lower body mass index (BMI) (t = −2.96, p = 0.003). ConclusionsBaseline orthostatic hypotension is a predictor of UPDRS motor decline in individuals with early PD and should be accounted for in clinical trial design. Low BMI may predict orthostatic hypotension in PD.

Orthostatic Hypotension in Parkinson's Disease: The Relation of Blood Pressure Tests and Symptoms in Daily Life.

Orthostatic hypotension (OH) is common in Parkinson's disease (PD), but the relation between the results of orthostatic blood pressure tests and orthostatic symptoms in daily life is not clear. We performed a cross-sectional study in an incident nontertiary care cohort of PD patients with additional recruitment of PD patients from our own outpatient clinic. We recruited sex- and age-matched controls. All participants underwent orthostatic blood pressure tests using continuous blood pressure measurements. Orthostatic symptoms experienced in daily life were assessed using autonomic symptom questionnaires (SCOPA-AUT and COMPASS-31). A total of 83 PD patients and 35 controls were included. Mean patient age was 69.2 years (standard deviation [SD]: 10.0). Mean disease duration was 6.6 years (SD, 0.8). The estimated prevalence of OH in PD was 24.1% (95% confidence interval: 16.2-34.3). There was no significant difference between PD patients with and without OH regarding reported daily orthostatic symptoms. Alternative OH criteria did not substantially improve this. Perceived orthostatic symptoms in daily life have no clear association with the results of a single orthostatic blood pressure test. Better diagnostic strategies are needed.

Elastic Abdominal Binders Attenuate Orthostatic Hypotension in Parkinson's Disease.

To investigate the possible efficacy of an elastic abdominal binder to control orthostatic hypotension (OH) associated with Parkinson's disease (PD), 15 patients with PD and OH were enrolled in a single-blind crossover study with elastic abdominal versus placebo binder on two different days, separated by a 1-day interval, followed by a 4-week open-label follow-up. Intervention significantly reduced blood pressure fall upon tilting. The mean difference (standard deviation; 95% confidence intervals) between abdominal binder versus placebo was +10 mm Hg (10.2; +3.5, +16.5; P = 0.006). No significant effect on supine mean blood pressure values was observed compared to placebo (P = 0.3). Symptoms of OH decreased significantly during follow-up (P = 0.003), as assessed by means of the Orthostatic Hypotension Questionnaire. Our findings suggest that elastic abdominal binders may be a simple complementary tool to alleviate OH in PD.

Identifying an Objective Benchmark to Initiate Pharmacologic Treatment of Orthostatic Hypotension in Parkinson Disease (P1.269)

Identifying an Objective Benchmark to Initiate Pharmacologic Treatment of Orthostatic Hypotension in Parkinson Disease (P1.269)

Orthostatic hypotension in Parkinson disease: how much you fall or how low you go?

Orthostatic hypotension (OH) is frequent in patients with Parkinson's disease (PD) and can occur with or without symptoms. Pharmacological treatments are effective, but often exacerbate supine hypertension. Guidelines exist for the diagnosis, but not for the treatment of OH. We examined the relationship between blood pressure (BP) and symptoms in a cohort of PD patients with the goal of identifying a hemodynamic target to guide treatment. We measured BP supine and upright (tilt or active standing) and identified the presence or absence of symptomatic OH by using a validated patient-reported outcome questionnaire in 210 patients with PD. We evaluated the usefulness of the 20/10 and 30/15 mmHg diagnostic criteria (systolic/diastolic) to identify symptomatic OH. Fifty percent of the PD patient cohort met criteria for the 20/10 fall and 30% for the 30/15 BP fall. Among the patients who met either OH criteria, the percentage of those with symptoms was small (33% of those with 20/10 and 44% of those with 30/15 mmHg; 16% and 13%, respectively, overall). Symptomatic OH was associated with an upright mean BP below 75 mmHg. A mean standing BP <75 mmHg had a sensitivity of 97% and a specificity of 98% for detecting symptomatic OH. Although the prevalence of OH in PD is high, not all patients have symptoms of organ hypoperfusion. A mean standing BP below 75 mmHg appears to be a useful benchmark when deciding whether the benefits of initiating pharmacological treatment of OH outweigh the risks of exacerbating supine hypertension.

Severity of orthostatic hypotension in the course of Parkinson's disease: no correlation with the duration of the disease.

Orthostatic hypotension (OH) is a common issue in Parkinson's disease (PD), affecting about 30%-40% of PD patients. Symptoms of OH include lightheadedness, dizziness, postural instability, vertigo and blurred vision. OH considerably contributes to disease burden and reduced quality of life for PD patients. To determine whether the severity of OH in PD advances significantly with the duration of the disease. For 106 PD patients lying-to-standing orthostatic tests were performed to evaluate orthostasis. Severity of OH was measured as maximal drop of systolic blood pressure (SBP) after postural challenge, as the mean of three measurements. The relationship between the maximal drop of SBP and the duration of PD was tested applying ANOVA. Consecutively, 64 patients under regular ambulant supervision received appointments to evaluate their orthostasis repeatedly. From these patients a separate cohort was set up to investigate OH progression in the course of PD. The lack of a correlation between the severity of OH in PD and the duration of the disease was determined (p = 0.064). The long term analysis for the patients under regular ambulant supervision demonstrated that the severity of OH does not advance in the course of PD in a statistically significant manner (p = 0.83). OH does not appear to be a symptom only of the late stage of PD. The presence of OH along with early motor signs does not necessarily point to multiple system atrophy.

Age and Orthostatic Hypotension in Parkinson Disease: Passive Tilt vs. Active Standing (P04.145)

Age and Orthostatic Hypotension in Parkinson Disease: Passive Tilt vs. Active Standing (P04.145)

Cognitive and MRI correlates of orthostatic hypotension in Parkinson’s disease

Orthostatic hypotension (OH) is a frequent nonmotor feature of Parkinson's disease (PD), and its occurrence has been associated with cognitive impairment. The underlying mechanism could be mediated by development of cerebrovascular disease induced by chronic or episodic hypoperfusion, but the extent of brain vascular load in PD patients with OH has never been investigated. This study aimed to assess the relationship between OH and cognitive function in PD patients and to investigate the contribution of brain vascular lesions. Forty-eight PD patients underwent a tilt table test (TT) to assess supine and orthostatic blood pressure as well as an extensive neuropsychological evaluation to evaluate cognitive function. Brain magnetic resonance imaging was acquired in 44/48 patients and analyzed by a visual semiquantitative scale. Twenty-three patients presented OH at TT (13/23 were symptomatic), and 25 did not. There were no differences in motor severity or disease duration between patients with and without OH. In patients with OH we found significantly worse cognitive performance in specific tasks, such as sustained attention, visuospatial and verbal memory, compared with patients without OH. However, there were no differences in vascular burden between the two groups. Our study confirms that there is an association between OH and selective cognitive deficits in PD, but rebuts the hypothesis that this is underlined by the development of cerebrovascular disease.

Biomarkers, Mechanisms, and Treatment of Autonomic Failure in Parkinson Disease and Related Disorders

Parkinson disease (PD) in one of the most common chronic neurodegenerative diseases of the elderly, and it is likely that as populations age PD will become even more prevalent and more of a public health burden. The movement disorder in PD is characterized by and likely results from severe depletion of dopaminergic neurons of the nigrostriatal system. By the time PD manifests clinically, most of the nigrostriatal dopaminergic neurons are already lost. Identifying laboratory measures—biomarkers—of the disease process is therefore crucial for advances in treatment and prevention. PD is often attended by signs or symptoms of impaired autonomic regulation of the circulation. This lecture comprehensively reviews and updates the field of autonomic cardiovascular abnormalities in PD and related disorders. About 30–40% of PD patients have orthostatic hypotension (OH). PD+OH is consistently associated with failure of both the cardiovagal and sympathoneural limbs of the arterial baroreflex, regardless of levodopa treatment. Most PD patients without OH have more subtle baroreflex abnormalities. Plasma levels of the sympathetic neurotransmitter norepinephrine (NE) and of dihydroxyphenylglycol, the main neuronal metabolite of NE, are lower in PD+OH than in PD without OH, indicating a relatively smaller overall complement of sympathetic nerves in PD+OH; however, patients with pure autonomic failure (PAF) have even lower NE and dihydroxyphenylglycol levels than do PD+OH patients, suggesting more extensive extra-cardiac noradrenergic denervation in PAF than in PD+OH. All patients with PD+OH have markedly reduced sympathetic noradrenergic innervation of the left ventricular myocardium. The cardiac neuroimaging findings in PD+OH contrast with those in multiple system atrophy (MSA), which can be difficult to distinguish from PD+OH, in that MSA usually entails intact sympathetic innervation of the heart. In PD patients with localized myocardial denervation there is earlier or more prominent involvement of the inferolateral wall than of the anterobasal septum, consistent with a retrograde, centripetal pathogenetic process. Cardiac sympathetic denervation occurs independently of striatal dopaminergic denervation across individual PD patients. Therefore, although cardiac sympathetic denervation invariably progresses over time in PD and can come on years before the motor disorder, the denervation can also be a late finding. Other non-motor manifestations such as olfactory dysfunction in PD are more closely associated with cardiac noradrenergic than with striatal dopaminergic denervation. PD and PAF feature not only decreased neuronal catecholamine uptake but also accelerated intra-neuronal catecholamine loss, which seems to reflect decreased vesicular uptake via the vesicular monoamine transporter. MSA patients have normal values for these parameters. In summary, baroreflex failure and cardiac and extra-cardiac noradrenergic denervation characterize OH in PD. These abnormalities occur independently of striatal dopamine depletion. Cardiovascular autonomic variables may provide biomarkers of pre-motor PD in some patients. Understanding mechanisms of cardiac sympathetic dysfunction and denervation in PD may also help elucidate bases of central catecholaminergic lesions in a variety of neurodegenerative diseases. In particular, Lewy body forms of alpha-synucleinopathy seem to be associated with decreased vesicular sequestration of cytosolic catecholamines, and since cytosolic catecholamines are toxic, decreased vesicular recycling may be part of a final pathogenetic pathway in the catecholaminergic denervation that characterizes these diseases.