How long you survive an α-synucleinopathy depends on which disorder struck you, according to a paper published online May 15 in JAMA Neurology. Scientists led by Rodolfo Savica and Michelle Mielke at the Mayo Clinic in Rochester, Minnesota, found that in a population-based sample, patients with α-synucleinopathies died younger than age-matched controls. The fastest killer was multiple system atrophy (MSA), followed by dementia with Lewy bodies (DLB), Parkinson’s disease with dementia (PDD), then Parkinson’s disease (PD). “These data are critical for clinicians counseling parkinsonism patients and caregivers, as it provides them with robust life expectancy estimates and may facilitate long-term care planning,” wrote Sirwan Darweesh, Erasmus MC University Medical Center Rotterdam, the Netherlands, to Alzforum.

Prior studies have reported survival rates for various parkinsonian disorders (see Elbaz et al., 2003; Driver et al., 2008; Goldstein et al., 2015); however, most of these recruited from hospitals rather than the general population, and none compared α-synucleinopathies side by side.

Savica and colleagues drew on medical records from the Rochester Epidemiology Project, which collates health data from all residents of Olmstead County, Minnesota. Between 1991 and 2010, 461 people were clinically diagnosed with a synucleinopathy accompanied by parkinsonism: 309 with PD, 81 with DLB, 55 with PDD, and 16 with MSA. Some people with MSA have a cerebellar form of disease without parkinsonism, but these patients were excluded. Each was compared to an age- and sex-matched control from the general population.

As a group, synucleinopathy patients died an average of two years younger than controls. Broken down by etiology, MSA took six years, DLB four years, PDD 3.5 years, and PD one year off a person’s lifespan. According to death certificates, neurodegenerative disease was the most common cause of death for people living with an α-synucleinopathy, listed at 32 percent. This was followed by cardiac events in 16 percent and cancer in 7 percent. Among controls, 26 percent died from a cardiac event and 18 percent from cancer. Interestingly, this adds to a growing number of studies that suggest patients with neurodegenerative disease have a lower risk of cancer (see May 2013 news; Tabarés-Seisdedos and Rubenstein, 2013).

Savica said that the difference in survival among the disorders could reflect different severities of disease and different rates and locations of α-synuclein deposition.

“The comparison of survival among different clinical phenotypes of synucleinopathies is new. It highlights the powerful effect of cognitive impairment and dementia to predict a poor prognosis across the PDD/DLB spectrum,” wrote David Irwin, University of Pennsylvania, Philadelphia, to Alzforum. “Further, there is limited data on the natural history of MSA, and this paper provides new insight into the relatively rapid progression of this disease.” He suggested that prospective studies following patients to autopsy could point to pathological variables that lead to longer or shorter survival in individual patients. Savica said his group has submitted one autopsy study for publication, and will expand on pathology in an upcoming project.

Both Irwin and Darweesh praised the population-based design. “As a result, the study’s patient sample is generally representative of the broad spectrum of underlying causes and clinical severity of synucleinopathy-associated parkinsonism in the community, ensuring that its findings can largely be generalized to similar populations,” wrote Darweesh.—Gwyneth Dickey Zakaib

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  1. These data are critical for clinicians counselling parkinsonism patients and caregivers, as they provide them with robust life expectancy estimates for patients and may facilitate long-term care planning. Important strengths of this study are its population-based design as well as its rigorous case-detection and ascertainment methods, which are particularly impressive in view of the wide scale of the study. As a result, the study’s patient sample is generally representative of the broad spectrum of underlying causes and clinical severity of synucleinopathy-associated parkinsonism in the community, ensuring that its findings can largely be generalized to similar populations.

  2. This is a very well-designed study and a strength is that they use a population-based approach with detailed clinical characterization of the patients identified from the medical record. The comparison of survival among different clinical phenotypes of synculeinopathies is new. It highlights the powerful effect of cognitive impairment and dementia to predict a poor prognosis across the PDD/DLB spectrum. Further, there is limited data on the natural history of MSA and this paper provides new insights into the relative rapid progression of this disease. Future prospective natural history studies following patients to autopsy will be important to define the neuropathological substrates that contribute to heterogeneity in survival on an individual patient level within each clinical phenotype.

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References

News Citations

  1. Skin Cancer Linked to Lower AD Risk—But Don't Hit the Beach Just Yet

Paper Citations

  1. . Survival study of Parkinson disease in Olmsted County, Minnesota. Arch Neurol. 2003 Jan;60(1):91-6. PubMed.
  2. . Parkinson disease and risk of mortality: a prospective comorbidity-matched cohort study. Neurology. 2008 Apr 15;70(16 Pt 2):1423-30. PubMed.
  3. . Survival in synucleinopathies: A prospective cohort study. Neurology. 2015 Nov 3;85(18):1554-61. Epub 2015 Oct 2 PubMed.
  4. . Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS disorders. Nat Rev Neurosci. 2013 Apr;14(4):293-304. PubMed.

Further Reading

Papers

  1. . Incidence and Pathology of Synucleinopathies and Tauopathies Related to Parkinsonism. JAMA Neurol. 2013 May 20;:1-7. PubMed.
  2. . Incidence of Dementia With Lewy Bodies and Parkinson Disease Dementia. JAMA Neurol. 2013 Sep 16; PubMed.

Primary Papers

  1. . Survival and Causes of Death Among People With Clinically Diagnosed Synucleinopathies With Parkinsonism: A Population-Based Study. JAMA Neurol. 2017 Jul 1;74(7):839-846. PubMed.