Mayo Clinic Proceedings Home

Survival and Progression in Synucleinopathy Phenotypes With Parkinsonism

A Population-Based Study



      To compare survival by the presenting parkinsonism symptoms at diagnosis among patients with incident clinically diagnosed synucleinopathies.

      Patients and Methods

      Using the Rochester Epidemiology Project medical records–linkage system, we identified all persons residing in Olmsted County, Minnesota, who received a diagnostic code of parkinsonism from January 1, 1991, through December 31, 2010. A movement disorder specialist reviewed the complete medical records of each individual to confirm the presence of parkinsonism, determine the type of synucleinopathy, and identify the onset dates of each cardinal symptom (tremor at rest, bradykinesia, rigidity, and impaired postural reflexes). We determined the median time from age at diagnosis to death or censoring (June 30, 2015) for each presenting symptom and the age- and sex-adjusted risk of death.


      From 1991 through 2010, a total of 433 individuals had a synucleinopathy diagnosed (301 [69.5%], Parkinson disease; 68 [15.7%], dementia with Lewy bodies; 52 [12.0%], Parkinson disease dementia; and 12 [2.8%], multiple systems atrophy with parkinsonism). Overall, the risk of death in the tremor-predominant group was less than that in the bradykinesia/rigidity-only group (hazard ratio [HR], 0.59; 95% CI, 0.40-0.87; P=.007). Similarly, risk of death in the bradykinesia/rigidity-only group was significantly greater than in the tremor-predominant group (HR, 1.75; 95% CI, 1.23-2.51; P=.002) and compared with tremor before bradykinesia (HR, 1.75; 95% CI, 1.24-2.47; P=.001).


      Patients with tremor as a presenting symptom have longer survival. In contrast, the presence of bradykinesia/rigidity as a presenting symptom correlates with reduced survival across all types of synucleinopathies.

      Abbreviations and Acronyms:

      DLB (dementia with Lewy bodies), HR (hazard ratio), MSA (multiple system atrophy), MSA-p (multiple system atrophy with parkinsonism), PD (Parkinson disease), PDD (Parkinson disease with dementia), PIGD (postural instability and gait difficulty)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Elbaz A.
        • Bower J.H.
        • Peterson B.J.
        • et al.
        Survival study of Parkinson disease in Olmsted County, Minnesota.
        Arch Neurol. 2003; 60: 91-96
        • Savica R.
        • Grossardt B.R.
        • Bower J.H.
        • Ahlskog J.E.
        • Rocca W.A.
        Incidence and pathology of synucleinopathies and tauopathies related to parkinsonism.
        JAMA Neurol. 2013; 70: 859-866
        • Savica R.
        • Grossardt B.R.
        • Bower J.H.
        • et al.
        Survival and causes of death among people with clinically diagnosed synucleinopathies with parkinsonism: a population-based study.
        JAMA Neurol. 2017; 74: 839-846
        • Figueroa J.J.
        • Singer W.
        • Parsaik A.
        • et al.
        Multiple system atrophy: prognostic indicators of survival.
        Mov Disord. 2014; 29: 1151-1157
        • Rajput A.H.
        • Pahwa R.
        • Pahwa P.
        • Rajput A.
        Prognostic significance of the onset mode in parkinsonism.
        Neurology. 1993; 43: 829-830
        • Savica R.
        • Grossardt B.R.
        • Bower J.H.
        • Boeve B.F.
        • Ahlskog J.E.
        • Rocca W.A.
        Incidence of dementia with Lewy bodies and Parkinson disease dementia.
        JAMA Neurol. 2013; 70: 1396-1402
        • St Sauver J.L.
        • Grossardt B.R.
        • Yawn B.P.
        • Melton 3rd, L.J.
        • Rocca W.A.
        Use of a medical records linkage system to enumerate a dynamic population over time: the Rochester epidemiology project.
        Am J Epidemiol. 2011; 173: 1059-1068
        • St Sauver J.L.
        • Grossardt B.R.
        • Leibson C.L.
        • Yawn B.P.
        • Melton 3rd, L.J.
        • Rocca W.A.
        Generalizability of epidemiological findings and public health decisions: an illustration from the Rochester epidemiology project.
        Mayo Clin Proc. 2012; 87: 151-160
        • Rocca W.A.
        • Yawn B.P.
        • St Sauver J.L.
        • Grossardt B.R.
        • Melton 3rd, L.J.
        History of the Rochester Epidemiology Project: half a century of medical records linkage in a US population.
        Mayo Clin Proc. 2012; 87: 1202-1213
        • St Sauver J.L.
        • Grossardt B.R.
        • Yawn B.P.
        • et al.
        Data resource profile: the Rochester Epidemiology Project (REP) medical records-linkage system.
        Int J Epidemiol. 2012; 41: 1614-1624
        • Commission on Professional and Hospital Activities; National Center for Health Statistics (U.S.)
        H-ICDA, Hospital Adaptation of ICDA.
        2nd ed. National Center for Health Statistics, Ann Arbor, MI1973
        • World Health Organization & International Conference for the Ninth Revision of the International Classification of Diseases
        Manual of the International Classification of Diseases, Injuries, and Causes of Death, based on the Recommendations of the Ninth Revision Conference, 1975, and Adopted by the Twenty-ninth World Health Assembly.
        World Health Organization, Geneva, Switzerland1977
        • Bower J.H.
        • Maraganore D.M.
        • McDonnell S.K.
        • Rocca W.A.
        Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990.
        Neurology. 1999; 52: 1214-1220
        • Collins S.J.
        • Ahlskog J.E.
        • Parisi J.E.
        • Maraganore D.M.
        Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria.
        J Neurol Neurosurg Psychiatry. 1995; 58: 167-173
        • Gilman S.
        • Low P.
        • Quinn N.
        • et al.
        Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology.
        Clin Auton Res. 1998; 8: 359-362
        • McKeith I.G.
        Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop.
        J Alzheimers Dis. 2006; 9: 417-423
        • Savica R.
        • Grossardt B.R.
        • Bower J.H.
        • Ahlskog J.E.
        • Rocca W.A.
        Risk factors for Parkinson's disease may differ in men and women: an exploratory study.
        Horm Behav. 2013; 63: 308-314
        • McKeith I.G.
        • Dickson D.W.
        • Lowe J.
        • et al.
        • Consortium on DLB
        Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.
        Neurology. 2005; 65: 1863-1872
        • Gilman S.
        • Wenning G.K.
        • Low P.A.
        • et al.
        Second consensus statement on the diagnosis of multiple system atrophy.
        Neurology. 2008; 71: 670-676
        • McKeith I.G.
        • Boeve B.F.
        • Dickson D.W.
        • et al.
        Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium.
        Neurology. 2017; 89: 88-100
        • Konno T.
        • Deutschlander A.
        • Heckman M.G.
        • et al.
        Comparison of clinical features among Parkinson's disease subtypes: a large retrospective study in a single center.
        J Neurol Sci. 2018; 386: 39-45
        • Lewis S.J.
        • Foltynie T.
        • Blackwell A.D.
        • Robbins T.W.
        • Owen A.M.
        • Barker R.A.
        Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach.
        J Neurol Neurosurg Psychiatry. 2005; 76: 343-348
        • Reijnders J.S.
        • Ehrt U.
        • Lousberg R.
        • Aarsland D.
        • Leentjens A.F.
        The association between motor subtypes and psychopathology in Parkinson's disease.
        Parkinsonism Relat Disord. 2009; 15: 379-382
        • van Rooden S.M.
        • Heiser W.J.
        • Kok J.N.
        • Verbaan D.
        • van Hilten J.J.
        • Marinus J.
        The identification of Parkinson's disease subtypes using cluster analysis: a systematic review.
        Mov Disord. 2010; 25: 969-978
        • Brimblecombe K.R.
        • Cragg S.J.
        The striosome and matrix compartments of the striatum: a path through the labyrinth from neurochemistry toward function.
        ACS Chem Neurosci. 2017; 8: 235-242
        • Kiss Z.H.
        • Mooney D.M.
        • Renaud L.
        • Hu B.
        Neuronal response to local electrical stimulation in rat thalamus: physiological implications for mechanisms of deep brain stimulation.
        Neuroscience. 2002; 113: 137-143
        • Obeso J.A.
        • Olanow C.W.
        • Rodriguez-Oroz M.C.
        • Krack P.
        • Kumar R.
        • Lang A.E.
        • Deep-Brain Stimulation for Parkinson's Disease Study Group
        Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease.
        N Engl J Med. 2001; 345: 956-963
        • Chu Y.
        • Kordower J.H.
        The prion hypothesis of Parkinson's disease.
        Curr Neurol Neurosci Rep. 2015; 15: 28
        • Schenkman M.
        • Moore C.G.
        • Kohrt W.M.
        • et al.
        Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson Disease: a phase 2 randomized clinical trial.
        JAMA Neurol. 2018; 75: 219-226
        • Sackett D.L.
        Bias in analytic research.
        J Chronic Dis. 1979; 32: 51-63