Cardiovascular autonomic dysfunction in dementia with Lewy bodies and Parkinson's disease

doi:10.1016/j.jns.2007.01.002

Journal of the Neurological Sciences

Volume 254, Issues 1–2, 15 March 2007, Pages 72-77

https://doi.org/10.1016/j.jns.2007.01.002 Get rights and content

Abstract

Objective

We estimated the extent and pattern of cardiovascular autonomic dysfunction in dementia with Lewy bodies (DLB) as compared with that in Parkinson's disease (PD).

Methods

We performed meta-iodobenzylguanidine (¹²³I-MIBG) scintigraphy of the heart and hemodynamic autonomic function testing using the Valsalva maneuver in 27 patients with DLB, 46 with PD, and 20 controls.

Results

¹²³I-MIBG uptakes in DLB were reduced as compared with those in control and PD. Hemodynamic studies revealed that DLB had decreased baroreceptor reflex and reduced responses of SBP in phases II and IV as compared with PD and control. SBP responses on standing and the difference in plasma norepinephrine (NE) concentrations between supine and standing positions were reduced in PD as compared with those in control. Furthermore, SBP responses on standing, plasma NE concentrations in supine and standing positions, and the difference in plasma NE concentrations between these positions were significantly lower in DLB than in PD and control. Plasma NE concentrations in DLB with orthostatic hypotension (OH) were lower than that in DLB without OH, although some patients who had DLB with orthostatic hypotension had relatively normal plasma NE levels.

Conclusion

Cardiovascular autonomic dysfunction is more severe in DLB than in PD and is usually caused by the loss of postganglionic sympathetic nervous function, although dysautonomia in some patients with DLB may result from preganglionic dysfunction.

Introduction

Dementia with Lewy bodies (DLB) is the second most common form of dementia in the elderly [1]. The Consortium on Dementia with Lewy Bodies described several core clinical features of DLB (recurrent visual hallucinations, fluctuating cognition, and spontaneous motor features of parkinsonism), as well as features that support the diagnosis (including repeated falls, syncope, transient loss of consciousness, and sensitivity to neuroleptic medications) [2]. Although repeated falls might be caused by disturbances of posture, gait, and balance particularly in patients with parkinsonism, syncope attacks suggest involvement of the brainstem and autonomic nervous system by Lewy bodies. Autonomic abnormalities such as orthostatic hypotension (OH) and carotid-sinus hypersensitivity often occur in patients with DLB and may increase the risk of repeated falls or episodes of syncope [3]. Autonomic failure may thus be a hallmark of DLB.

Neuropathological features of DLB include widespread neuronal degeneration associated with Lewy bodies containing α-synuclein [4]. DLB is considered a distinct clinicopathological entity and is classified as an α-synucleinopathy, similar to idiopathic Parkinson's disease (PD) [4]. In patients with PD, Lewy bodies are found mainly in the brain stem; autonomic symptoms frequently coexist with core motor impairments, such as tremor, extremity rigidity, bradykinesia, and postural instability. For instance, OH affects from 20% to 50% of patients with PD [5], [6], [7], [8], [9], [10]. However, autonomic function in DLB has received little attention and has not been studied systematically [11], [12], [13]. The severity of autonomic dysfunction in DLB is intermediate between that of multiple system atrophy (MSA) and PD [14]. Nonetheless, autonomic failure, especially cardiovascular dysautonomia, in DLB remains poorly understood.

The objective of our study was to quantitatively assess autonomic dysfunction, especially involving the cardiovascular system in DLB. We also attempted to differentiate between DLB and PD on the basis of cardiovascular autonomic involvement, because DLB has a distinct clinical course and progresses more rapidly than PD [15].

To evaluate cardiovascular autonomic dysfunction in DLB, we performed meta-iodobenzylguanidine (¹²³I-MIBG) scintigraphy of the heart and hemodynamic autonomic function testing using the Valsalva maneuver. We also assessed blood pressure changes on head-up tilt-table testing. The results in patients with DLB were compared with those in patients with PD and control subjects.

Section snippets

Study groups

The subjects were 27 patients with DLB, 46 patients with PD, and 20 controls with no neurological disorders (Table 1). Patients with DLB or PD who had undergone autonomic testing at Aoto Hospital in Jikei University School of Medicine from 1999 through 2004 were identified and reviewed for the study.

A diagnosis of clinically probable DLB required progressive cognitive decline with two of the following features: 1) fluctuating cognition or arousal, 2) recurrent visual hallucinations, and 3)

¹²³I-MIBG uptake scintigraphy

H/M ratios for early and delayed images were significantly lower in PD than in control. Early and delayed H/M ratios were significantly lower in DLB than in PD or control (Table 2).

Cardiovascular autonomic function tests

BRS II and IVp were significantly lower in PD than in control (BRSII: PD 2.1 ± 0.9 vs control 4.3 ± 1.9, p < 0.001; IVp: PD 15.2 ± 8.1 vs control 21.6 ± 6.9, p < 0.005). BRS IV and IIp were similar in PD and control (BRS IV: PD 5.3 ± 3.1 vs control 6.4 ± 1.5, ns; IIp: PD 9.4 ± 7.2 vs control 11.8 ± 4.9, ns). BRS II, BRS IV, IIp, and IVp

Discussion

Our study showed that cardiac ¹²³I-MIBG uptake in DLB was significantly lower than that in control and PD. ¹²³I-MIBG has been used clinically as an index of myocardial sympathetic nerve damage to assess efferent postganglionic neuronal function in the heart [23], [24]. Our findings suggested that cardiac sympathetic dysfunction is more severe in patients with DLB than in those with PD. The severely reduced cardiac MIBG uptake in DLB relative to that in PD might be due to greater postganglionic

References (39)

H. Oka et al.
Cardiovascular dysautonomia in de novo Parkinson's disease
J Neurol Sci
(2006)
J. Kautzner et al.
Arterial baroreflex sensitivity assessed from phase IV of the Valsalva maneuver
Am J Cardio
(1996)
M. Suzuki et al.
Impaired myocardial ¹²³I-metaiodobenzylguanidine uptake in Lewy body disease: comparison between dementia with Lewy bodies and Parkinson's disease
J Neurol Sci
(2006)
E.I. Elisberg et al.
The effect of the Valsalva maneuver on the circulation. II. The role of the autonomic nervous system in the production of the overshoot
Am Heart J
(1953)
P.G. Guyenet et al.
Role of medulla oblongata in generation of sympathetic and vagal outflows
Prog Brain Res
(1996)
I.G. McKeith et al.
Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop
Neurology
(1996)
I.G. McKeith et al.
Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium
Neurology
(2005)
R.A. Kenny et al.
Carotid sinus syndrome is common in dementia with Lewy bodies and correlates with deep white matter lesions
J Neurol Neurosurg Psychiatry
(2004)
J.L. Cummings
Dementia with Lewy bodies: molecular pathogenesis and implications for classification
J Geriatr Psychiatry Neurol
(2004)
C.G. Goetz et al.
Autonomic dysfunction in Parkinson's disease
Neurology
(1986)

D.S. Goldstein et al.

Cardiac sympathetic denervation in Parkinson disease

Ann Intern Med

(2000)

Y. Niimi et al.

Clinical and physiological characteristics of autonomic failure with Parkinson's disease

Clinic Auton Res

(1999)

C. Rostagno et al.

Decreased baroreflex sensitivity assessed from phase IV of Valsalva maneuver in mild cognitive heart failure

Angiology

(1999)

G.K. Wenning et al.

Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study

J Neurol Neurosurg Psychiatry

(1999)

J.M. Senard et al.

Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management

Drugs Aging

(2001)

K.R. Chaudhuri

Autonomic dysfunction in movement disorders

Curr Opin Neurol

(2001)

Y. Horimoto et al.

Autonomic dysfunctions in dementia with Lewy bodies

J Neurol

(2003)

A.S. Pakiam et al.

Diffuse Lewy body disease presenting as multiple system atrophy

Can J Neurol Sci

(1999)

P. Thaisetthawatkul et al.

Autonomic dysfunction in dementia with Lewy body disease

Neurology

(2004)

Cited by (54)

The role of the autonomic nervous system in cerebral blood flow regulation in dementia: A review
2022, Autonomic Neuroscience: Basic and Clinical
In this review we will examine the role of the autonomic nervous system in the control of cerebral blood flow (CBF) in dementia. Worldwide, 55 million people currently live with dementia, and this figure will increase as the global population ages. Understanding the changes in vascular physiology in dementia could pave the way for novel therapeutic approaches. Reductions in CBF have been demonstrated in multiple dementia sub-types, in addition to increased cerebrovascular resistance and reduced vasoreactivity. Cerebral autoregulation (CA) is a key mechanism for the maintenance of cerebral perfusion, but remains largely intact in cognitive disorders, despite reductions in global and regional CBF. However, the tight coupling between neuronal activity and CBF (neurovascular coupling - NVC) is lost in dementia, which may be a key driver of cognitive dysfunction. Despite numerous studies investigating disturbances in the control of CBF in dementia, less is known about the specific mechanisms responsible for the observed changes. Disturbances could be related to one of a number of pathways and mechanisms including disruption of the autonomic component. In this review we will explore clinical and animal studies, which specifically investigated the autonomic component of CBF control in dementia, drawing on the clinical implications and potential for novel biomarker and therapeutic targets.
Autonomic dysfunction: Diagnosis and management
2019, Handbook of Clinical Neurology
The autonomic nervous system is designed to maintain physiologic homeostasis. Its widespread connections make it vulnerable to disruption by many disease processes including primary etiologies such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, and pure autonomic failure and secondary etiologies such as diabetes mellitus, amyloidosis, and immune-mediated illnesses. The result is numerous symptoms involving the cardiovascular, gastrointestinal, and urogenital systems. Patients with autonomic dysfunction (AUD) often have peripheral and/or cardiac denervation leading to impairment of the baroreflex, which is known to play a major role in determining hemodynamic outcome during orthostatic stress and low cardiac output states. Heart rate and plasma norepinephrine responses to orthostatic stress are helpful in diagnosing impairment of the baroreflex in patients with orthostatic hypotension (OH) and suspected AUD. Similarly, cardiac sympathetic denervation diagnosed with MIBG scintigraphy or ¹⁸F-DA PET scanning has also been shown to be helpful in distinguishing preganglionic from postganglionic involvement and in diagnosing early stages of neurodegenerative diseases. In this chapter, we review the causes of AUD, the pathophysiology and resulting cardiovascular manifestations with emphasis on the diagnosis and treatment of OH.
Favorable Effect of Sympathetic Nervous Activity on Rehabilitation Outcomes in Frail Elderly
2015, Journal of the American Medical Directors Association
Previous studies have suggested the relationship between physical function, mortality, and autonomic nervous activity in frail elderly and that maintaining sympathetic nervous activity might lead to improved physical function and mortality in the elderly population. The aim of this study was to investigate the utility of sympathetic nervous activity measured by heart rate variability in frail elderly patients undergoing inpatient rehabilitation, further focusing the nervous activity on the effect of rehabilitation therapy.
Prospective cohort study.
Sixty-one subjects aged 75 years or older were recruited after treatment of acute phase illness.
Before undergoing rehabilitation, data of 24-hour Holter monitoring and a blood venous sample were obtained. From RR intervals in the electrocardiogram, heart rate and SDs of all NN intervals in all 5-minute segments of the entire recording, power spectral density, low frequency (LF), high frequency (HF), and low frequency/high frequency (LF/HF) were calculated. Functional Independence Measure (FIM) and Barthel index were used to measure physical function.
FIM score and Barthel index were 46.8 ± 25.4 and 32.8 ± 31.7, respectively. Serum total protein, albumin, hemoglobin, and total cholesterol were all significantly related to FIM score and Barthel index before rehabilitation. Heart rate variability indices did not show a significant relationship with physical function, whereas the high LH/HF group showed significant improvement in physical function compared with the low LH/HF group. Moreover, LF/HF frequency was a predictive factor for improvement of physical function after 2 months of rehabilitation.
A favorable effect of preserved LF/HF on rehabilitation outcome was observed in elderly undergoing rehabilitation. Preservation of sympathetic nervous activity may lead to improved physical function in the elderly.
Orthostatic Hypotension and Orthostatic Intolerance
2015, Endocrinology: Adult and Pediatric
Rapid eye movement sleep behavior disorder as a biomarker for neurodegeneration: The past 10years
2013, Sleep Medicine
Citation Excerpt :
Autonomic symptoms and signs are common in PD, related to synuclein deposition in the dorsal motor vagus [19], and in peripheral postganglionic sympathetic tissues at earliest stages of PD [20,21]. These abnormalities are also often seen in DLB, and cardiac denervation may even be more severe in DLB than PD [22,23]. There has been some population-based evidence that autonomic dysfunction can predict PD.
Since its original description, idiopathic rapid eye movement sleep behavior disorder (RBD) has become a well-established risk factor for neurodegenerative disease. Studies from sleep centers have found that at least 40–65% of patients with idiopathic RBD will develop a defined neurodegenerative phenotype over 10 years. This elevated risk of neurodegeneration has been recently confirmed in a population-based study of probable RBD. When a defined syndrome develops, it is almost always a ‘synucleinopathy’ (Parkinson’s disease, Dementia with Lewy Bodies or multiple system atrophy). Often, manifestations of parkinsonism and cognitive impairment overlap. The ability of RBD to predict disease has major implications for development of neuroprotective therapy. First, RBD is a prodromal marker with a disease risk sufficiently high for design of neuroprotective trials. Second, study of idiopathic RBD allows prospective testing of other predictive markers of neurodegeneration. Third, it allows an unprecedented direct examination of the evolution of prodromal disease into defined neurodegenerative syndromes. This review summarizes what is known about the risk of neurodegeneration in idiopathic RBD, the utility of prodromal/predictive markers in synuclein-mediated neurodegeneration, and the evolution of motor and non-motor markers in prodromal stages.
Neurochemistry and the non-motor aspects of PD
2012, Neurobiology of Disease
Parkinson disease (PD) is a systemic disease with variegated non-motor deficits and neurological symptoms, including impaired olfaction, autonomic failure, cognitive impairment and psychiatric symptoms, in addition to the classical motor symptoms. Many non-motor symptoms appear before or in parallel with motor deficits and then worsen with disease progression. Although there is a relationship, albeit not causal, between motor symptoms and the presence of Lewy bodies (LBs) and neurites filled with abnormal α-synuclein, other neurological alterations are independent of the amount of α-synuclein inclusions in neurons and neurites, thereby indicating that different mechanisms probably converge in the degenerative process. This may apply to complex alterations interfering with olfactory and autonomic nervous system functions, emotions, sleep regulation, and behavioral, cognitive and mental performance. Involvement of the cerebral cortex leading to impaired behavior and cognition is related to several convergent altered factors including: a. dopaminergic, noradrenergic, serotoninergic and cholinergic cortical innervation; b. synapses; c. cortical metabolism; d. mitochondrial function and energy production; e. oxidative damage; f. transcription; g. protein expression; h. lipid composition; and i. ubiquitin–proteasome system and autophagy, among others. This complex situation indicates that multiple subcellular failure in selected cell populations is difficult to reconcile with a reductionistic scenario of a single causative cascade of events leading to non-motor symptoms in PD. Furthermore, these alterations may appear at early stages of the disease and may precede the appearance of substantial irreversible cell loss by years. These observations have important implications in the design of therapeutic approaches geared to prevention and treatment of PD.

View all citing articles on Scopus

View full text

Cardiovascular autonomic dysfunction in dementia with Lewy bodies and Parkinson's disease

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Study groups

123I-MIBG uptake scintigraphy

Cardiovascular autonomic function tests

Discussion

J Neurol Sci

Am J Cardio

J Neurol Sci

Am Heart J

Prog Brain Res

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop

Neurology

Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium

Neurology

Carotid sinus syndrome is common in dementia with Lewy bodies and correlates with deep white matter lesions

J Neurol Neurosurg Psychiatry

Dementia with Lewy bodies: molecular pathogenesis and implications for classification

J Geriatr Psychiatry Neurol

Autonomic dysfunction in Parkinson's disease

Neurology

Cardiac sympathetic denervation in Parkinson disease

Ann Intern Med

Clinical and physiological characteristics of autonomic failure with Parkinson's disease

Clinic Auton Res

Decreased baroreflex sensitivity assessed from phase IV of Valsalva maneuver in mild cognitive heart failure

Angiology

Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study

J Neurol Neurosurg Psychiatry

Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management

Drugs Aging

Autonomic dysfunction in movement disorders

Curr Opin Neurol

Autonomic dysfunctions in dementia with Lewy bodies

J Neurol

Diffuse Lewy body disease presenting as multiple system atrophy

Can J Neurol Sci

Autonomic dysfunction in dementia with Lewy body disease

Neurology

¹²³I-MIBG uptake scintigraphy