Association of Autonomic Dysfunction With Disease Progression and Survival in Parkinson Disease | Movement Disorders | JAMA Neurology | JAMA Network
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1.
Lewis  SJ, Foltynie  T, Blackwell  AD, Robbins  TW, Owen  AM, Barker  RA.  Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach.  J Neurol Neurosurg Psychiatry. 2005;76(3):343-348.PubMedGoogle ScholarCrossref
2.
Marras  C, Chaudhuri  KR.  Nonmotor features of Parkinson’s disease subtypes.  Mov Disord. 2016;31(8):1095-1102.PubMedGoogle ScholarCrossref
3.
van Rooden  SM, Heiser  WJ, Kok  JN, Verbaan  D, van Hilten  JJ, Marinus  J.  The identification of Parkinson’s disease subtypes using cluster analysis: a systematic review.  Mov Disord. 2010;25(8):969-978.PubMedGoogle ScholarCrossref
4.
Post  B, Merkus  MP, de Haan  RJ, Speelman  JD. Prognostic factors for the progression of Parkinson's disease: a systematic review. Mov Disord. 2007;22(13):1839-1851, quiz 1988.
5.
van der Heeden  JF, Marinus  J, Martinez-Martin  P, Rodriguez-Blazquez  C, Geraedts  VJ, van Hilten  JJ.  Postural instability and gait are associated with severity and prognosis of Parkinson disease.  Neurology. 2016;86(24):2243-2250.PubMedGoogle ScholarCrossref
6.
Macleod  AD, Taylor  KS, Counsell  CE.  Mortality in Parkinson’s disease: a systematic review and meta-analysis.  Mov Disord. 2014;29(13):1615-1622.PubMedGoogle ScholarCrossref
7.
Asahina  M, Vichayanrat  E, Low  DA, Iodice  V, Mathias  CJ.  Autonomic dysfunction in parkinsonian disorders: assessment and pathophysiology.  J Neurol Neurosurg Psychiatry. 2013;84(6):674-680.PubMedGoogle ScholarCrossref
8.
Tada  M, Onodera  O, Tada  M,  et al.  Early development of autonomic dysfunction may predict poor prognosis in patients with multiple system atrophy.  Arch Neurol. 2007;64(2):256-260.PubMedGoogle ScholarCrossref
9.
Low  PA, Reich  SG, Jankovic  J,  et al.  Natural history of multiple system atrophy in the USA: a prospective cohort study.  Lancet Neurol. 2015;14(7):710-719.PubMedGoogle ScholarCrossref
10.
Watanabe  H, Saito  Y, Terao  S,  et al.  Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients.  Brain. 2002;125(Pt 5):1070-1083.PubMedGoogle ScholarCrossref
11.
O’Sullivan  SS, Massey  LA, Williams  DR,  et al.  Clinical outcomes of progressive supranuclear palsy and multiple system atrophy.  Brain. 2008;131(pt 5):1362-1372.PubMedGoogle ScholarCrossref
12.
Petrovic  IN, Ling  H, Asi  Y,  et al.  Multiple system atrophy–parkinsonism with slow progression and prolonged survival: a diagnostic catch.  Mov Disord. 2012;27(9):1186-1190.PubMedGoogle ScholarCrossref
13.
Stubendorff  K, Aarsland  D, Minthon  L, Londos  E.  The impact of autonomic dysfunction on survival in patients with dementia with Lewy bodies and Parkinson’s disease with dementia.  PLoS One. 2012;7(10):e45451.PubMedGoogle ScholarCrossref
14.
McKeith  IG, Dickson  DW, Lowe  J,  et al; Consortium on DLB.  Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.  Neurology. 2005;65(12):1863-1872.PubMedGoogle ScholarCrossref
15.
Abrams  P, Cardozo  L, Fall  M,  et al; Standardisation Sub-committee of the International Continence Society.  The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society.  Neurourol Urodyn. 2002;21(2):167-178.PubMedGoogle ScholarCrossref
16.
Tomlinson  CL, Stowe  R, Patel  S, Rick  C, Gray  R, Clarke  CE.  Systematic review of levodopa dose equivalency reporting in Parkinson’s disease.  Mov Disord. 2010;25(15):2649-2653.PubMedGoogle ScholarCrossref
17.
Rothman  KJ.  No adjustments are needed for multiple comparisons.  Epidemiology. 1990;1(1):43-46.PubMedGoogle ScholarCrossref
18.
Perneger  TV.  What’s wrong with Bonferroni adjustments.  BMJ. 1998;316(7139):1236-1238.PubMedGoogle ScholarCrossref
19.
Gray  WK, Wood  BH, Walker  RW.  Do autonomic function tests in people with Parkinson’s disease predict survival rates at 7 years follow-up?  Mov Disord. 2009;24(16):2432-2434.PubMedGoogle Scholar
20.
de Lau  LM, Verbaan  D, Marinus  J, van Hilten  JJ.  Survival in Parkinson’s disease: relation with motor and non-motor features.  Parkinsonism Relat Disord. 2014;20(6):613-616.PubMedGoogle ScholarCrossref
21.
Goldstein  DS, Holmes  C, Sharabi  Y, Wu  T.  Survival in synucleinopathies: a prospective cohort study.  Neurology. 2015;85(18):1554-1561.PubMedGoogle ScholarCrossref
22.
Allcock  LM, Kenny  RA, Burn  DJ.  Clinical phenotype of subjects with Parkinson’s disease and orthostatic hypotension: autonomic symptom and demographic comparison.  Mov Disord. 2006;21(11):1851-1855.PubMedGoogle ScholarCrossref
23.
Müller  B, Larsen  JP, Wentzel-Larsen  T, Skeie  GO, Tysnes  OB; Parkwest Study Group.  Autonomic and sensory symptoms and signs in incident, untreated Parkinson’s disease: frequent but mild.  Mov Disord. 2011;26(1):65-72.PubMedGoogle ScholarCrossref
24.
van Rooden  SM, Colas  F, Martínez-Martín  P,  et al.  Clinical subtypes of Parkinson’s disease.  Mov Disord. 2011;26(1):51-58.PubMedGoogle ScholarCrossref
25.
Fereshtehnejad  SM, Romenets  SR, Anang  JB, Latreille  V, Gagnon  JF, Postuma  RB.  New clinical subtypes of Parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes.  JAMA Neurol. 2015;72(8):863-873.PubMedGoogle ScholarCrossref
26.
Anang  JB, Gagnon  JF, Bertrand  JA,  et al.  Predictors of dementia in Parkinson disease: a prospective cohort study.  Neurology. 2014;83(14):1253-1260.PubMedGoogle ScholarCrossref
27.
de Lau  LM, Verbaan  D, van Rooden  SM, Marinus  J, van Hilten  JJ.  Relation of clinical subtypes in Parkinson’s disease with survival.  Mov Disord. 2014;29(1):150-151.PubMedGoogle ScholarCrossref
28.
van Dijk  JG, Haan  J, Zwinderman  K, Kremer  B, van Hilten  BJ, Roos  RA.  Autonomic nervous system dysfunction in Parkinson’s disease: relationships with age, medication, duration, and severity.  J Neurol Neurosurg Psychiatry. 1993;56(10):1090-1095.PubMedGoogle ScholarCrossref
Original Investigation
August 2017

Association of Autonomic Dysfunction With Disease Progression and Survival in Parkinson Disease

Author Affiliations
  • 1Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, United Kingdom
  • 2Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, London, United Kingdom
  • 3Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom
JAMA Neurol. 2017;74(8):970-976. doi:10.1001/jamaneurol.2017.1125
Key Points

Question  Is development of autonomic dysfunction associated with disease progression and survival in patients with Parkinson disease?

Findings  In this study of 100 patients with autopsy-confirmed Parkinson disease, earlier development of autonomic dysfunction was associated with an increase in the risk of reaching a disease milestone of 14% per year and an increase in the risk of death of 8% per year.

Meaning  Earlier autonomic dysfunction is associated with more rapid disease progression and shorter survival in patients with Parkinson disease.

Abstract

Importance  Evidence suggests that development of autonomic dysfunction (AutD) may negatively affect disease course and survival in patients with synucleinopathies. However, the few available studies on Parkinson disease (PD) have conflicting results, comprise a small number of patients, have short follow-up periods, and lack pathologic confirmation of the diagnosis.

Objective  To examine the association of time of onset of AutD with disease progression and survival in PD.

Design, Setting, and Participants  This retrospective review of clinical data from 100 consecutive patients with an autopsy-confirmed diagnosis of PD from the archives of the Queen Square Brain Bank in London, United Kingdom, from January 1, 2006, to June 3, 2016, included patients with PD regularly seen by hospital specialists (neurologists or geriatricians) in the United Kingdom throughout their disease until death. Patients with dementia before or within 1 year after onset of motor symptoms, monogenic forms of PD, comorbidities that affect autonomic function, a coexisting neuropathologic diagnosis, or insufficient clinical information were excluded.

Main Outcomes and Measures  Survival and time from diagnosis to specific disease milestones were calculated to assess disease progression. Autonomic dysfunction was defined as autonomic failure at autonomic function testing or 2 of the following symptoms: urinary symptoms, constipation, upper gastrointestinal tract dysfunction, orthostatic hypotension, sweating abnormalities, or erectile dysfunction. Multivariable Cox proportional hazards regression models on the risk of a disease milestone and death were used.

Results  A total of 100 patients (60 [60.0%] male; mean [SD] age at diagnosis, 63.9 [10.3] years; mean [SD] disease duration, 14.6 [7.7] years) were studied. Autonomic dysfunction developed in 85 patients (mean [SD] time from diagnosis, 6.7 [7.7] years) and was associated with older age at diagnosis, male sex, poor initial levodopa treatment response, and postural instability and gait difficulty motor PD subtype in linear regression analysis, but staging of α-synuclein pathologic changes was unrelated. Earlier AutD increased the risk of reaching the first milestone (hazard ratio, 0.86; 95% CI, 0.83-0.89; P < .001) and shortened survival (hazard ratio, 0.92; 95% CI, 0.88-0.96; P < .001). Older age at diagnosis and poorer levodopa treatment response were the other factors associated with shorter survival in adjusted multivariate analysis.

Conclusions and Relevance  Earlier AutD is associated with a more rapid development of disease milestones and shorter survival in patients with PD.

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