Autonomic dysfunction in Parkinson's disease: A prospective cohort study

Merola, Aristide; Romagnolo, Alberto; Rosso, Michela; Suri, Ritika; Berndt, Zoe; Maule, Simona; Lopiano, Leonardo; Espay, Alberto J.

doi:10.1002/mds.27268

Cited by 125 publications

(115 citation statements)

References 38 publications

(46 reference statements)

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“…A previous study reported that up to 40% of PD patients with autonomic dysfunction were “asymptomatic,” and even “asymptomatic” autonomic dysfunction caused higher prevalence of falls, worsened activities of daily life (ADL) and affected their quality of life (QOL) . In a follow up study , the severity of autonomic symptoms progressed by 20% over the course of a year and was independently associated with impairment in ADLs and QOL. Symptomatic and asymptomatic OH were both associated with increased falls and health care utilization.…”

Section: Discussionmentioning

confidence: 99%

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Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction

et al. 2019

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We performed a clinicopathological study to assess the burden of small vessel disease (SVD) type of pathological changes in elderly demented subjects, who had clinical evidence of autonomic dysfunction, either carotid sinus hypersensitivity or orthostatic hypotension or both or had exhibited unexpected repeated falls. Clinical and neuropathological diagnoses in 112 demented subjects comprised dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Alzheimer's disease (AD), Mixed dementia (mostly AD‐DLB) and vascular dementia (VaD). Of these, 12 DLB subjects had no recorded unexpected falls in life and therefore no evidence of concomitant autonomic dysfunction. A further 17 subjects were assessed as aging controls without significant pathology or signs of autonomic dysfunction. We quantified brain vascular pathological changes and determined severities of neurodegenerative lesions including α‐synuclein pathology. We found moderate‐severe vascular changes and high‐vascular pathology scores (P < 0.01) in all neurodegenerative dementias and as expected in VaD compared to similar age controls. Arteriolosclerosis, perivascular spacing and microinfarcts were frequent in the basal ganglia and frontal white matter (WM) across all dementias, whereas small infarcts (<5 mm) were restricted to VaD. In a sub‐set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (P < 0.02). Sclerotic index values were increased by ~50% in both the WM and neocortex in all dementias compared to similar age controls. We found no evidence for increased α‐synuclein deposition in subjects with autonomic dysfunction. Our findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction. SVD changes may not necessarily manifest in clinically overt symptoms but they likely confound motor or cognitive dysfunction. We propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging‐related neurodegenerative disorders and characterize their end‐stage clinical syndromes.

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Section: Discussionmentioning

confidence: 99%

“…OH develops in nearly 50% of Parkinsonians and may be present in over 90% of PDD patients . OH is an independent risk for incident dementia and often accompanied by disabling symptoms, impaired quality of life, dizziness, nausea, sweating and loss of consciousness .…”

Section: Introductionmentioning

confidence: 99%

Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction

et al. 2019

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“…The motor function abnormalities associated with PD are well known, but patients with PD also experience nonmotor symptoms that can precede the onset of motor dysfunctions (Pont-Sunyer et al 2015), such as those produced by autonomic or cardiovascular system dysfunction (Goldstein et al 2005;Vianna et al 2016). Taken together, these impairments greatly impact patient-perceived quality of life (Kluger et al 2016;Merola et al 2018;Wolters 2009).…”

Section: Introductionmentioning

confidence: 99%

Blunted cardiovascular responses to exercise in Parkinson’s disease patients: role of the muscle metaboreflex

Sabino‐Carvalho

Teixeira

Samora

et al. 2018

Journal of Neurophysiology

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Patients with Parkinson's disease (PD) exhibit attenuated cardiovascular responses to exercise. The underlying mechanisms that are potentially contributing to these impairments are not fully understood. Therefore, we sought to test the hypothesis that patients with PD exhibit blunted cardiovascular responses to isolated muscle metaboreflex activation following exercise. For this, mean blood pressure, cardiac output, and total peripheral resistance were measured using finger photoplethysmography and the Modelflow method in 11 patients with PD [66 ± 2 yr; Hoehn and Yahr score: 2 ± 1 a.u.; time since diagnosis: 7 ± 1 yr; means ± SD) and 9 age-matched controls (66 ± 3 yr). Measurements were obtained at rest, during isometric handgrip exercise performed at 40% maximal voluntary contraction, and during postexercise ischemia. Also, a cold pressor test was assessed to confirm that blunted cardiovascular responses were specific to exercise and not representative of generalized sympathetic responsiveness. Changes in mean blood pressure were attenuated in patients with PD during handgrip (PD: ∆25 ± 2 mmHg vs. controls: ∆31 ± 3 mmHg; P < 0.05), and these group differences remained during postexercise ischemia (∆17 ± 1 mmHg vs. ∆26 ± 1 mmHg, respectively; P < 0.01). Additionally, changes in total peripheral resistance were attenuated during exercise and postexercise ischemia, indicating blunted reflex vasoconstriction in patients with PD. Responses to cold pressor test did not differ between groups, suggesting no group differences in generalized sympathetic responsiveness. Our results support the concept that attenuated cardiovascular responses to exercise observed in patients with PD are, at least in part, explained by an altered skeletal muscle metaboreflex. NEW & NOTEWORTHY Patients with Parkinson's disease (PD) presented blunted cardiovascular responses to exercise. We showed that cardiovascular response evoked by the metabolic component of the exercise pressor reflex is blunted in patients with PD. Furthermore, patients with PD presented similar pressor response during the cold pressor test compared with age-matched controls. Altogether, our results support the hypothesis that attenuated cardiovascular responses to exercise observed in patients with PD are mediate by an altered skeletal muscle metaboreflex.

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“…A multicenter study including 1,021 PD patients in Japan has reported the following prevalence rates of various non-motor symptoms of PD: constipation, 79.6%; urinary problems, 65.9%; and lightheadedness upon standing, 44.1% [8]. A recent prospective study showed that the worsening of autonomic symptoms was independently associated with deterioration in daily living activities and quality of life in patients with PD [6]. Therefore, a thorough evaluation of the autonomic symptoms in patients with PD is important but requires time and special equipment.…”

Section: Introductionmentioning

confidence: 99%

“…Autonomic symptoms, including gastrointestinal, urinary and cardiovascular dysfunction are reported in 20-80% of PD patients [2][3][4][5] and these symptoms significantly impact their quality of life [6]. Constipation and urinary problems are common autonomic impairments that are often difficult to treat in PD.…”

Section: Introductionmentioning

confidence: 99%

Autonomic Symptoms Correlate with Non-Autonomic Non-Motor Symptoms and Sleep Problems in Patients with Parkinson’s Disease

et al. 2018

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Objective: The objective of this study was to clarify the relationship between autonomic and non-autonomic non-motor symptoms in patients with Parkinson’s disease (PD). Methods: Sixty-five PD patients were included in this study (27 men and 38 women; aged 68.5 ± 10.0; Hoehn and Yahr (HY) stage 2.6 ± 1.1). The autonomic symptoms were evaluated by the Japanese version of the Scales for outcomes in PD autonomic (SCOPA-AUT) questionnaire. The patients were assessed with the mini-mental state examination (MMSE), PD sleep evaluation scale-2 (PDSS-2), Epworth sleepiness scale (ESS) and Beck’s depression inventory II (BDI-II). The Non-Motor Symptom Scale (NMSS) total scores and subscores of non-autonomic non-motor symptom domains (sleep/fatigue, mood/cognition, perceptual problems/hallucination, and attention/memory) were evaluated. A dopamine transporter (DAT) scan, metaiodobenzylguanidine (MIBG) myocardial scintigraphy, and card type olfactory identification test (open essence [OE, Wako]) were performed. Results: The SCOPA-AUT total score was positively correlated with the disease duration, HY stage, levodopa equivalent dose, PDSS-2, ESS, BDI-II and non-autonomic NMSS and inversely correlated with the MMSE. The high-SCOPA-AUT group (≥9) had lower MMSE scores and higher PDSS-2, ESS, BDI-II and non-motor NMSS scores than the low-SCOPA-AUT group (< 9). The DAT scan, MIBG uptake and OE score did not differ between the groups. In a stepwise linear regression analysis, which excluded possibly overlapping items among the scales, the subtotals of PDSS-2 items, except for item 8 (nocturia), (p < 0.0001) and non-autonomic NMSS domains (p = 0.00040) were significant predictors of the total SCOPA-AUT score. Conclusion: Our study shows significant correlations among autonomic symptoms, PD-related sleep problems and non-autonomic non-motor symptoms in PD patients.

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Autonomic dysfunction in Parkinson's disease: A prospective cohort study

Cited by 125 publications

References 38 publications

Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction

Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction

Blunted cardiovascular responses to exercise in Parkinson’s disease patients: role of the muscle metaboreflex

Autonomic Symptoms Correlate with Non-Autonomic Non-Motor Symptoms and Sleep Problems in Patients with Parkinson’s Disease

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