Delayed orthostatic hypotension in Parkinson’s disease

Yoo, Sang‐Won; Kim, Joong‐Seok; Yoo, Ji-Yeon; Yun, Eunkyeong; Yoon, Uicheul; Shin, Na‐Young; Lee, Kwang Soo

doi:10.1038/s41531-021-00181-y

Cited by 17 publications

(26 citation statements)

References 41 publications

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“…Orthostatic hypotension can cause syncope and falls 16 and fall-related fractures, pneumonia, and even death. Some autonomic symptoms, such as constipation, can occur in the early stage of disease and may even precede the onset of motor symptoms by many years 16 , 17 . We speculate that both dopaminergic and adrenergic neurons in the nigrostriatal and peripheral nervous systems are lost progressively with the gradual worsening of motor and non-motor symptoms.…”

Section: Discussionmentioning

confidence: 99%

Corneal confocal microscopy differentiates patients with Parkinson’s disease with and without autonomic involvement

Che

Chen

Jiang

et al. 2022

npj Parkinsons Dis.

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Autonomic dysregulation in Parkinson’s disease (PD) can precede motor deficits and is associated with reduced quality of life, disease progression, and increased mortality. Objective markers of autonomic involvement in PD are limited. Corneal confocal microscopy (CCM) is a rapid ophthalmic technique that can quantify small nerve damage in a range of peripheral and autonomic neuropathies. Here we investigated whether CCM can be used to assess autonomic symptoms in PD. Based on the scale for outcomes in Parkinson’s disease for autonomic symptoms (SCOPA-AUT), patients with PD were classified into those without autonomic symptoms (AutD-N), with single (AutD-S), and multiple (AutD-M) domain autonomic dysfunction. Corneal nerve fiber pathology was quantified using CCM, and the relationship with autonomic symptoms was explored. The study enrolled 71 PD patients and 30 control subjects. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and CNBD/CNFD ratio were lower in PD patients with autonomic symptoms compared to those without autonomic symptoms. Autonomic symptoms correlated positively with CNFD (r = −0.350, p = 0.004), and were not related to Levodopa equivalent daily dose (r = 0.042, p = 0.733) after adjusting for age, disease severity, disease duration or cognitive function. CCM parameters had high sensitivity and specificity in distinguishing patients with PD with and without autonomic symptoms. PD patients with autonomic symptoms have corneal nerve loss, and CCM could serve as an objective ophthalmic imaging technique to identify patients with PD and autonomic symptoms.

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Section: Discussionmentioning

confidence: 99%

Corneal confocal microscopy differentiates patients with Parkinson’s disease with and without autonomic involvement

Che

Chen

Jiang

et al. 2022

npj Parkinsons Dis.

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“…2 PD + OH patients were slightly older and had a higher supine systolic BP compared to PD No-OH patients, as reported by previous studies. 9,15 This suggests that PD + OH patients could have suffered greater cerebral hemodynamic insult due to wider BP uctuations. 16 Each caudate nucleus was signi cantly correlated to multiple ipsilateral regions.…”

Section: Discussionmentioning

confidence: 99%

Caudate-anchored cognitive connectivity pursuant to orthostatic hypotension in early Parkinson disease

Yoo

et al. 2022

Preprint

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18F-Florbetaben is a tracer used to evaluate the metabolic activity of and amyloid accumulation in the brain when measured in early- and late-phase, respectively. The metabolism of neural substrates could be viewed as a network and might be an important factor in cognition. Orthostatic hypotension (OH) might play an indirect moderating role in cognition, and its latent influence could modify the inherent cognitive network. This study aimed to identify changes of cognitive connectivity according to orthostatic stress in patients with early Parkinson’s disease (PD). This study included 104 early PD patients who were evaluated with a head-up tilt-test and 18F-Florbetaben positron emission tomography (PET). Cognition was assessed with a comprehensive neuropsychological battery that gauged attention/working memory, language, visuospatial, memory, and executive functions. PET images were analyzed visually for amyloid deposits, and early-phase images were normalized to obtain standardized uptake ratios (SUVRs) of pre-specified subregions relevant to specific cognitive domains. The caudate nucleus was referenced and paired to these pre-specified regions. The correlations between SUVRs of these regions were assessed and stratified according to presence of orthostatic hypotension. Among the patients studied, 22 (21.2%) participants had orthostatic hypotension. Nineteen patients (18.3%) were positive for amyloid-𝛽 accumulation upon visual analysis. Moderate correlations between the caudate and pre-specified subregions were observed (Spearman’s rho, range [0.331–0.545]). Cognition did not differ, but the patterns of correlation were altered when the disease was stratified by presence of orthostatic stress. In conclusion, cognition in early PD responds to hemodynamic stress by adapting its neural connections between regions relevant to cognitive functions.

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“…Falls can lead to injury, decreased activity due to fear of falling, poor quality of life, and caregiver stress ( LeWitt et al, 2019 ). Studies have shown that OH can happen in the early stages of the disease and may occur with or without symptoms ( Palma et al, 2015 ; Cutsforth-Gregory and Low 2019 ; Yoo et al, 2021 ). In this study, we investigated the involvement of the cardiac baroreflex and cardio-postural coupling (hypothesized reflex muscle-pump function) in maintaining blood pressure in Parkinson’s patients and healthy controls during an orthostatic challenge induced via a head-up tilt test.…”

Section: Introductionmentioning

confidence: 99%

Effect of Parkinson’s Disease on Cardio-postural Coupling During Orthostatic Challenge

et al. 2022

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Cardiac baroreflex and leg muscles activation are two important mechanisms for blood pressure regulation, failure of which could result in syncope and falls. Parkinson’s disease is known to be associated with cardiac baroreflex impairment and skeletal muscle dysfunction contributing to falls. However, the mechanical effect of leg muscles contractions on blood pressure (muscle-pump) and the baroreflex-like responses of leg muscles to blood pressure changes is yet to be comprehensively investigated. In this study, we examined the involvement of the cardiac baroreflex and this hypothesized reflex muscle-pump function (cardio-postural coupling) to maintain blood pressure in Parkinson’s patients and healthy controls during an orthostatic challenge induced via a head-up tilt test. We also studied the mechanical effect of the heart and leg muscles contractions on blood pressure. We recorded electrocardiogram blood pressure and electromyogram from 21 patients with Parkinson’s disease and 18 age-matched healthy controls during supine, head-up tilt at 70°, and standing positions with eyes open. The interaction and bidirectional causalities between the cardiovascular and musculoskeletal signals were studied using wavelet transform coherence and convergent cross mapping techniques, respectively. Parkinson’s patients displayed an impaired cardiac baroreflex and a reduced mechanical effect of the heart on blood pressure during supine, tilt and standing positions. However, the effectiveness of the cardiac baroreflex decreased in both Parkinson’s patients and healthy controls during standing as compared to supine. In addition, Parkinson’s patients demonstrated cardio-postural coupling impairment along with a mechanical muscle pump dysfunction which both could lead to dizziness and falls. Moreover, the cardiac baroreflex had a limited effect on blood pressure during standing while lower limb muscles continued to contract and maintain blood pressure via the muscle-pump mechanism. The study findings highlighted altered bidirectional coupling between heart rate and blood pressure, as well as between muscle activity and blood pressure in Parkinson’s disease. The outcomes of this study could assist in the development of appropriate physical exercise programs to reduce falls in Parkinson’s disease by monitoring the cardiac baroreflex and cardio-postural coupling effect on maintaining blood pressure.

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Delayed orthostatic hypotension in Parkinson’s disease

Cited by 17 publications

References 41 publications

Corneal confocal microscopy differentiates patients with Parkinson’s disease with and without autonomic involvement

Corneal confocal microscopy differentiates patients with Parkinson’s disease with and without autonomic involvement

Caudate-anchored cognitive connectivity pursuant to orthostatic hypotension in early Parkinson disease

Effect of Parkinson’s Disease on Cardio-postural Coupling During Orthostatic Challenge

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